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  • 51.
    Bounechada, Djamela
    et al.
    Chalmers, Dept Chem & Biol Engn, SE-41296 Gothenburg, Sweden Chalmers, Competence Ctr Catalysis, SE-41296 Gothenburg, Sweden .
    Darmastuti, Zhafira
    Linköping University, Department of Physics, Chemistry and Biology, Applied Sensor Science. Linköping University, The Institute of Technology.
    Andersson, Mike
    Linköping University, Department of Physics, Chemistry and Biology, Applied Sensor Science. Linköping University, The Institute of Technology.
    Ojamäe, Lars
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Lloyd Spetz, Anita
    Linköping University, Department of Physics, Chemistry and Biology, Applied Sensor Science. Linköping University, The Institute of Technology.
    Skoglundh, Magnus
    Chalmers, Dept Chem & Biol Engn, SE-41296 Gothenburg, Sweden Chalmers, Competence Ctr Catalysis, SE-41296 Gothenburg, Sweden.
    Carlsson, Per-Anders
    Chalmers, Dept Chem & Biol Engn, SE-41296 Gothenburg, Sweden Chalmers, Competence Ctr Catalysis, SE-41296 Gothenburg, Sweden.
    Vibrational Study of SOx Adsorption on Pt/SiO22014In: The Journal of Physical Chemistry C, ISSN 1932-7447, E-ISSN 1932-7455, Vol. 118, no 51, p. 29713-29723Article in journal (Refereed)
    Abstract [en]

    The formation of ad-SOx species on Pt/SiO2 upon exposure to SO2 in concentrations ranging from 10 to 50 ppm at between 200 and 400 degrees C has been studied by in situ diffuse reflectance infrared Fourier transformed spectroscopy. In parallel, first-principles calculations have been carried out to consolidate the experimental interpretations. It was found that sulfate species form on the silica surface with a concomitant removal/rearrangement of silanol groups. Formation of ad-SOx species occurs only after SO2 oxidation to SO3 on the platinum surface. Thus, SO2 oxidation to SO3 is the first step in the SOx adsorption process, followed by spillover of SO3 to the oxide, and finally, the formation of sulfate species on the hydroxyl positions on the oxide. The sulfate formation is influenced by both temperature and SO2 concentration. Furthermore, exposure to hydrogen is shown to be sufficiently efficient as to remove ad-SOx species from the silica surface.

  • 52.
    Bounechada, Djamela
    et al.
    Chalmers Institute of Technology, Gothenburg.
    Darmastuti, Zhafira
    Linköping University, Department of Physics, Chemistry and Biology, Applied Sensor Science. Linköping University, The Institute of Technology.
    Ojamae, Lars
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Andersson, Mike
    Linköping University, Department of Physics, Chemistry and Biology, Applied Sensor Science. Linköping University, The Institute of Technology.
    Lloyd Spetz, Anita
    Linköping University, Department of Physics, Chemistry and Biology, Applied Sensor Science. Linköping University, The Institute of Technology.
    Skoglundh, Magnus
    Competence Centre for Catalysis / Department of Chemical and Biological Engineering, Chalmers University of Technology, Göteborg, Sweden.
    Carlsson, P-A
    Competence Centre for Catalysis / Department of Chemical and Biological Engineering, Chalmers University of Technology, Göteborg, Sweden.
    Vibrational analysis of SO2 on Pt / SiO2 systemManuscript (preprint) (Other academic)
    Abstract [en]

    In situ diffuse reflectance infrared Fourier transformed spectroscopy was used to study the interactions of SOx species with Pt/SiO2 between 200 and 400°C, and for SO2 concentrations between 10 and 50 ppm, which represents a concentration range where MISFET sensors exhibit good responses. In parallel, first-principles calculations have been carried out to support the experimental interpretations. It was found that sulfate species were formed on the silica surface, accompanied with removal/rearrangement of silanol groups upon exposure to SO2. Both experimental and theoretical calculations also suggest that the surface species were only formed after SO2 oxidation to SO3 on the metal surface. These evidences support the idea of SO2 oxidation to SO3 as the first step in the process of sulfate formation, followed by spillover of SO3 to the oxide, and finally the formation of sulfate species on the hydroxyl positions on the oxide. The results also indicate that the sulfate formation on silica depends both on the temperature and the SO2 concentration. Furthermore, hydrogen exposure was shown to be efficient for sulfur removal from the silica surface.

  • 53.
    Boyd, Robert
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Plasma and Coating Physics. Linköping University, Faculty of Science & Engineering.
    Söderlind, Fredrik
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Helmersson, Ulf
    Linköping University, Department of Physics, Chemistry and Biology, Plasma and Coating Physics. Linköping University, Faculty of Science & Engineering.
    Odén, Magnus
    Linköping University, Department of Physics, Chemistry and Biology, Nanostructured Materials. Linköping University, Faculty of Science & Engineering.
    Pilch, Iris
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Complex 3D nanocoral like structures formed by copper nanoparticle aggregation on nanostructured zinc oxide rods2016In: Materials letters (General ed.), ISSN 0167-577X, E-ISSN 1873-4979, Vol. 184, p. 127-130Article in journal (Refereed)
    Abstract [en]

    This paper reports a new strategy for nanoparticle surface assembly so that they form anisotropic fibril like features, consisting of particles directly attached to each other, which can extend 500 nm from the surface. The particles are both formed and deposited in a single step process enabled via the use of a pulsed plasma based technique. Using this approach, we have successfully modified zinc oxide rods, up to several hundred nanometers in diameter, with 25 nm diameter copper nanoparticles for catalytic applications. The resulting structure could be modelled using a diffusion limited aggregation based approach. This gives the material the appearance of marine coral, hence the term nanocoral. (C) 2016 Elsevier B.V. All rights reserved.

  • 54.
    Brelstaff, Jack
    et al.
    University of Cambridge, England.
    Ossola, Bernardino
    University of Cambridge, England.
    Neher, Jonas J.
    University of Tubingen, Germany.
    Klingstedt, Therese
    MRC, England.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Goedert, Michel
    MRC, England.
    Grazia Spillantini, Maria
    University of Cambridge, England.
    Tolkovsky, Aviva M.
    University of Cambridge, England.
    The fluorescent pentameric oligothiophene pFTAA identifies filamentous tau in live neurons cultured from adult P301S tau mice2015In: Frontiers in Neuroscience, ISSN 1662-4548, E-ISSN 1662-453X, Vol. 9, no 184Article in journal (Refereed)
    Abstract [en]

    Identification of fluorescent dyes that label the filamentous protein aggregates characteristic of neurodegenerative disease, such as beta-amyloid and tau in Alzheimers disease, in a live cell culture system has previously been a major hurdle. Here we show that pentameric formyl thiophene acetic acid (pFTAA) fulfills this function in living neurons cultured from adult P301S tau transgenic mice. Injection of pFTAA into 5-month-old P301S tau mice detected cortical and DRG neurons immunoreactive for AT100, an antibody that identifies solely filamentous tau, or MC1, an antibody that identifies a conformational change in tau that is commensurate with neurofibrillary tangle formation in Alzheimers disease brains. In fixed cultures of dorsal root ganglion (DRG) neurons, pFTAA binding, which also identified AT100 or MC1+ve neurons, followed a single, saturable binding curve with a half saturation constant of 0.14 mu M, the first reported measurement of a binding affinity of a beta-sheet reactive dye to primary neurons harboring filamentous tau. Treatment with formic acid, which solubilizes filamentous tau, extracted pFTAA, and prevented the re-binding of pFTAA and MC1 without perturbing expression of soluble tau, detected using an anti-human tau (HT7) antibody. In live cultures, pFTAA only identified DRG neurons that, after fixation, were AT100/MC1+ve, confirming that these forms of tau pre-exist in live neurons. The utility of pFTAA to discriminate between living neurons containing filamentous tau from other neurons is demonstrated by showing that more pFTAA+ve neurons die than pFTAA-ve neurons over 25 days. Since pFTAA identifies fibrillar tau and other misfolded proteins in living neurons in culture and in animal models of several neurodegenerative diseases, as well as in human brains, it will have considerable application in sorting out disease mechanisms and in identifying diseasemodifying drugs that will ultimately help establish the mechanisms of neurodegeneration in human neurodegenerative diseases.

  • 55.
    Buchholt, Kristina
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Ieva, E.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry.
    Käll, Per-Olov
    Linköping University, Department of Physics, Chemistry and Biology, Physical Chemistry. Linköping University, The Institute of Technology.
    Ojamäe, Lars
    Linköping University, Department of Physics, Chemistry and Biology, Physical Chemistry. Linköping University, The Institute of Technology.
    Torsi, L
    Universita degli Studi di Bari, Italy.
    Lutic, D.
    Växjö universitet.
    Strand, M
    Växjö universitet.
    Sanati, M.
    Växjö universitet.
    Lloyd Spetz, Anita
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    FET devices with gold nanoparticle gate material as nitrogen oxide gas sensors2006In: Proceedings from E-MRS 2006, Nice France, May 29- June 1, 2006, 2006, p. 87-92Conference paper (Refereed)
    Abstract [en]

       

  • 56.
    Burns, R. E.
    et al.
    University of Calif San Diego, CA 92103 USA.
    Gaffney, P. M.
    University of Calif San Diego, CA 92103 USA.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Armien, A. G.
    University of Minnesota, MN 55108 USA.
    Pessier, A. P.
    University of Calif San Diego, CA 92103 USA.
    Systemic Amyloidosis in an African Tiger Snake (Telescopus semiannulatus)2017In: Journal of Comparative Pathology, ISSN 0021-9975, E-ISSN 1532-3129, Vol. 157, no 2-3, p. 136-140Article in journal (Refereed)
    Abstract [en]

    An adult male African tiger snake (Telescopts semiannulatus) was diagnosed with disseminated mycobacteriosis and a hepatic biliary cystadenocarcinoma. Histologically, the spleen was largely replaced by extracellular deposits of eosinophilic, fibrillar to hyaline material. Similar material was also present in the testicular interstitium and occasional blood vessel walls. This material was congophilic with strong green birefringence under polarized light and emitted fluorescence when bound to the luminescent-conjugated oligothiophene, h-FTAA, an amyloid binding probe. Ultrastructurally, deposits were composed of aggregates of haphazardly arranged, non-branching fibrils up to 8 nm in diameter and of indeterminate length. These findings all supported a diagnosis of amyloidosis, most likely amyloid A (AA) type based on concurrent inflammatory disease in this snake. However, immunohistochemistry for serum amyloid A was negative. There are only rare previous reports of amyloidosis in reptiles and many have been incompletely characterized. This case presents a thorough investigation into an occurrence of systemic amyloidosis in a snake, including a novel use of luminescent-conjugated oligothiophene binding in a reptile to confirm the diagnosis. (C) 2017 Elsevier Ltd. All rights reserved.

  • 57.
    Buttera, Sydney C.
    et al.
    Carleton University, Canada.
    Ronnby, Karl
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Science & Engineering.
    Pedersen, Henrik
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Ojamäe, Lars
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Barry, Sean T.
    Carleton University, Canada.
    Thermal study of an indium trisguanidinate as a possible indium nitride precursor2018In: Journal of Vacuum Science & Technology. A. Vacuum, Surfaces, and Films, ISSN 0734-2101, E-ISSN 1520-8559, Vol. 36, no 1, article id 01A101Article in journal (Refereed)
    Abstract [en]

    Tris-N,N,-dimethyl-N,N -diisopropylguanidinatoindium(III) has been investigated both as a chemical vapor deposition precursor and an atomic layer deposition precursor. Although deposition was satisfactory in both cases, each report showed some anomalies in the thermal stability of this compound, warrenting further investigation, which is reported herein. The compound was found to decompose to produce diisopropylcarbodiimide both by computational modeling and solution phase nuclear magnetic resonance characterization. The decomposition was shown to have an onset at approximately 120 degrees C and had a constant rate of decomposition from 150 to 180 degrees C. The ultimate decomposition product was suspected to be bisdimethylamidoN, N,-dimethyl-N,N -diisopropylguanidinato-indium(III), which appeared to be an intractable, nonvolatile polymer. Published by the AVS.

  • 58.
    Bäck, Marcus
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Appelqvist, Hanna
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    LeVine, Harry III
    University of Kentucky, KY 40536 USA.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Anionic Oligothiophenes Compete for Binding of X-34 but not PIB to Recombinant A beta Amyloid Fibrils and Alzheimers Disease Brain-Derived A beta2016In: CHEMISTRY-A EUROPEAN JOURNAL, ISSN 0947-6539, Vol. 22, no 51, p. 18335-18338Article in journal (Refereed)
    Abstract [en]

    Deposits comprised of amyloid- (A) are one of the pathological hallmarks of Alzheimers disease (AD) and small hydrophobic ligands targeting these aggregated species are used clinically for the diagnosis of AD. Herein, we observed that anionic oligothiophenes efficiently displaced X-34, a Congo Red analogue, but not Pittsburgh compoundB (PIB) from recombinant A amyloid fibrils and Alzheimers disease brain-derived A. Overall, we foresee that the oligothiophene scaffold offers the possibility to develop novel high-affinity ligands for A pathology only found in human AD brain, targeting a different site than PIB.

  • 59.
    Campos Melo, Raul Ivan
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Studies on molecular aspects of Transthyretin Amyloidosis2015Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Proteins are versatile molecules that play a variety of roles in maintaining the human body, e.g. transport of nutrients. Transthyretin (TTR) is a 55 kDa homotetrameric protein found in human plasma and in the cerebrospinal fluid, responsible for the transport of retinol (vitamin A) and T4 (thyroxine). This protein is probably not essential for life, since TTR knockout mice have normal fetal development and lifespan. TTR, like 25 other human proteins, has been associated to the deposition of amyloid aggregates. Previous research has shown that mutations considerably increase the propensity of the protein to form aggregates. However, the wild type protein also exhibits this ability to aggregate, giving rise to the senile systemic amyloidosis disease that affects 20% people over 80 years of age. It is well accepted that self-association of monomeric subunits triggers the disease through tetramer dissociation, since stabilization of the quaternary structure suppresses aggregate formation.

    However, a detailed description of the self-assembly mechanism and fibril structure remains unresolved. Here, using a combination of primarily small -angle X-ray scattering (SAXS) and hydrogen exchange mass spectrometry analysis, we describe an unexpectedly dynamic TTR protofibril structure which exchanges protomers with highly unfolded monomers in solution. With SAXS, we reveal the continuous presence of a considerably unfolded TTR monomer throughout the fibrillation process, and show that a considerable fraction of the fibrillating protein remains in solution even at a late maturation state.

    In our efforts to study both native and protofibrillar TTR, we realized the need for development of a fluorescent small molecule capable of binding native and protofibrillar TTR, providing distinguishable emission spectra. We used microwave heating for efficient synthesis and fluorescence spectral screening of compounds. We synthesized and tested 22 analogs displaying a variety of functional groups, most of them linked to a stilbene scaffold. We successfully developed two compounds that detect both TTR states at physiological concentrations. The compounds bound with nM-μM affinities and displayed very distinct emission maxima upon binding native or protofibrillar TTR (> 100 nm difference).

    We expect these new findings regarding protofibril self-assembly mechanism, together with our novel molecules serve as important tools in future studies of TTR amyloid formation.

    List of papers
    1. Considerably Unfolded Transthyretin Monomers Preceed and Exchange with Dynamically Structured Amyloid Protofibrils
    Open this publication in new window or tab >>Considerably Unfolded Transthyretin Monomers Preceed and Exchange with Dynamically Structured Amyloid Protofibrils
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    2015 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, no 11443Article in journal (Refereed) Published
    Abstract [en]

    Despite numerous studies, a detailed description of the transthyretin (TTR) self-assembly mechanism and fibril structure in TTR amyloidoses remains unresolved. Here, using a combination of primarily small -angle X-ray scattering (SAXS) and hydrogen exchange mass spectrometry (HXMS) analysis, we describe an unexpectedly dynamic TTR protofibril structure which exchanges protomers with highly unfolded monomers in solution. The protofibrils only grow to an approximate final size of 2,900 kDa and a length of 70 nm and a comparative HXMS analysis of native and aggregated samples revealed a much higher average solvent exposure of TTR upon fibrillation. With SAXS, we reveal the continuous presence of a considerably unfolded TTR monomer throughout the fibrillation process, and show that a considerable fraction of the fibrillating protein remains in solution even at a late maturation state. Together, these data reveal that the fibrillar state interchanges with the solution state. Accordingly, we suggest that TTR fibrillation proceeds via addition of considerably unfolded monomers, and the continuous presence of amyloidogenic structures near the protofibril surface offers a plausible explanation for secondary nucleation. We argue that the presence of such dynamic structural equilibria must impact future therapeutic development strategies.

    Place, publisher, year, edition, pages
    Nature Publishing Group: Open Access Journals - Option C / Nature Publishing Group, 2015
    National Category
    Chemical Sciences
    Identifiers
    urn:nbn:se:liu:diva-120227 (URN)10.1038/srep11443 (DOI)000356857900001 ()26108284 (PubMedID)
    Note

    Funding Agencies|This work was funded by the Danish Council for Independent Research, Medical Sciences; Danish Council for Independent Research, Medical Sciences, Sapere Aude programme; Drug Research Academy; DANSCATT; Swedish Research Council; Linux cluster at University of Copenhagen by the Carlsberg Research Foundation; FTIR spectrophotometer by the Apotekerfonden

    Available from: 2015-07-21 Created: 2015-07-20 Last updated: 2018-04-25
    2. Novel Trans-Stilbene-based Fluorophores as Probes for Spectral Discrimination of Native and Protofibrillar Transthyretin
    Open this publication in new window or tab >>Novel Trans-Stilbene-based Fluorophores as Probes for Spectral Discrimination of Native and Protofibrillar Transthyretin
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    2016 (English)In: ACS Chemical Neuroscience, ISSN 1948-7193, E-ISSN 1948-7193, Vol. 7, no 7, p. 924-940Article in journal (Refereed) Published
    Abstract [en]

    Accumulation of misfolded transthyretin (TTR) as amyloid fibrils causes various human disorders. Native transthyretin is a neurotrophic protein and is a putative extracellular molecular chaperone. Several fluorophores have been shown in vitro to bind selectively to native TTR. Other compounds, such as thioflavin T, bind TTR amyloid fibrils. The probe 1-anilinonaphthalene-8-sulfonate (ANS) binds to both native and fibrillar TTR, becoming highly fluorescent, but with indistinguishable emission spectra for native and fibrillar TTR. Herein we report our efforts to develop a fluorescent small molecule capable of binding both native and misfolded protofibrillar TTR, providing distinguishable emission spectra. We used microwave synthesis for efficient production of a small library of trans-stilbenes and fluorescence spectral screening of their binding properties. We synthesized and tested 22 trans-stilbenes displaying a variety of functional groups. We successfully developed two naphthyl-based trans-stilbenes probes that detect both TTR states at physiological concentrations. The compounds bound with nanomolar to micromolar affinities and displayed distinct emission maxima upon binding native or misfolded protofibrillar TTR (>100 nm difference). The probes were mainly responsive to environment polarity providing evidence for the divergent hydrophobic structure of the binding sites of these protein conformational states. Furthermore, we were able to successfully use one of these probes to quantify the relative amounts of native and protofibrillar TTR in a dynamic equilibrium. In conclusion, we identified two trans-stilbene-based fluorescent probes, (E)-4-(2-(naphthalen-1-yl)vinyl)benzene-1,2-diol (11) and (E)-4-(2-(naphthalen-2-yl)vinyl)benzene-1,2-diol (14), that bind native and protofibrillar TTR, providing a wide difference in emission maxima allowing conformational discrimination by fluorescence spectroscopy. We expect these novel molecules to serve as important chemical biology research tools in studies of TTR folding and misfolding.

    Place, publisher, year, edition, pages
    American Chemical Society (ACS), 2016
    Keywords
    transthyretin, amyloid, stilbene, fluorescence, probe, spectrum
    National Category
    Chemical Sciences
    Identifiers
    urn:nbn:se:liu:diva-122842 (URN)10.1021/acschemneuro.6b00062 (DOI)000380297500009 ()27144293 (PubMedID)
    Note

    At the time for thesis presentation publication was in status: Manuscript

    Funding agencies:The work was supported by Goran Gustafsson's Foundation (PH), The Swedish Research Council (PH), The Linkoping center for systemic neuroscience, LiU-Neuro, (XW), and Sven and Lilly Lawski's foundation (ME).

    Available from: 2015-11-26 Created: 2015-11-26 Last updated: 2018-04-25Bibliographically approved
  • 60.
    Campos Melo, Raúl Ivan
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Wu, Xiongyu
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Elgland, Mathias
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Konradsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Hammarström, Per
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Novel Trans-Stilbene-based Fluorophores as Probes for Spectral Discrimination of Native and Protofibrillar Transthyretin2016In: ACS Chemical Neuroscience, ISSN 1948-7193, E-ISSN 1948-7193, Vol. 7, no 7, p. 924-940Article in journal (Refereed)
    Abstract [en]

    Accumulation of misfolded transthyretin (TTR) as amyloid fibrils causes various human disorders. Native transthyretin is a neurotrophic protein and is a putative extracellular molecular chaperone. Several fluorophores have been shown in vitro to bind selectively to native TTR. Other compounds, such as thioflavin T, bind TTR amyloid fibrils. The probe 1-anilinonaphthalene-8-sulfonate (ANS) binds to both native and fibrillar TTR, becoming highly fluorescent, but with indistinguishable emission spectra for native and fibrillar TTR. Herein we report our efforts to develop a fluorescent small molecule capable of binding both native and misfolded protofibrillar TTR, providing distinguishable emission spectra. We used microwave synthesis for efficient production of a small library of trans-stilbenes and fluorescence spectral screening of their binding properties. We synthesized and tested 22 trans-stilbenes displaying a variety of functional groups. We successfully developed two naphthyl-based trans-stilbenes probes that detect both TTR states at physiological concentrations. The compounds bound with nanomolar to micromolar affinities and displayed distinct emission maxima upon binding native or misfolded protofibrillar TTR (>100 nm difference). The probes were mainly responsive to environment polarity providing evidence for the divergent hydrophobic structure of the binding sites of these protein conformational states. Furthermore, we were able to successfully use one of these probes to quantify the relative amounts of native and protofibrillar TTR in a dynamic equilibrium. In conclusion, we identified two trans-stilbene-based fluorescent probes, (E)-4-(2-(naphthalen-1-yl)vinyl)benzene-1,2-diol (11) and (E)-4-(2-(naphthalen-2-yl)vinyl)benzene-1,2-diol (14), that bind native and protofibrillar TTR, providing a wide difference in emission maxima allowing conformational discrimination by fluorescence spectroscopy. We expect these novel molecules to serve as important chemical biology research tools in studies of TTR folding and misfolding.

  • 61.
    Carlsson, Anders
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Identification of potential plasma biomarkers of inflammation in farmers with musculoskeletal disorders: A proteomic study2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    In this thesis we look for potential chronic inflammation biomarkers because studies have shown that farmers with musculoskeletal disorders might be affected by the environment to develop musculoskeletal disorders. Animal farmers are highly exposed to dust, aerosols, molds and other toxins in the air and environment leading to musculoskeletal disorders, respiratory disorders, airway symptoms and febrile reactions. There is reason to believe that the farmers have a constant or chronic inflammation that develops into musculoskeletal disorders. By using a proteomic approach with Two-dimensional Gel Electrophoresis and silver staining our goal was to find biomarkers by quantifying protein spots that differ significantly from farmers with musculoskeletal disorders compared to rural controls. In our study we found 8 significant proteins, two from Alpha-2-HS-glycoprotein, one from Apolipoprotein A1, three from Haptoglobin, one from Hemopexin and 1 from Antithrombin. All 5 proteins are involved in inflammation response in some way and some proteins are linked to chronic inflammation. Out of the 5 proteins Alpha-2-HS-glycoprotein, Apolipoprotein A1 and Hemopexin seem like the most likely proteins to investigate further as potential inflammation biomarkers.

  • 62.
    Carlsson, Andreas
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering. Swedish National Forens Centre NFC, Linkoping, Sweden.
    Synthesis and spectroscopic characterization of emerging synthetic cannabinoids and cathinones2016Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    The application of different analytical techniques is fundamental in forensic drug analysis. In the wake of the occurrence of large numbers of new psychoactive substances possessing similar chemical structures as already known ones, focus has been placed on applied criteria for their univocal identification. These criteria vary, obviously, depending on the applied technique and analytical approach. However, when two or more substances are proven to have similar analytical properties, these criteria no longer apply, which imply that complementary techniques have to be used in their differentiation.

    This work describes the synthesis of some structural analogues to synthetic cannabinoids and cathinones based on the evolving patterns in the illicit drug market. Six synthetic cannabinoids and six synthetic cathinones were synthesized, that, at the time for this study, were not as yet found in drug seizures. Further, a selection of their spectroscopic data is compared to those of already existing analogues; mainly isomers and homologues. The applied techniques were mass spectrometry (MS), Fourier transformed infrared (FTIR, gas phase) spectroscopy and nuclear magnetic resonance (NMR) spectroscopy. In total, 59 different compounds were analyzed with the  selected techniques.

    The results from comparison of spectroscopic data showed that isomeric substances may in some cases be difficult to unambiguously identify based only on their GC-MS EI spectra. On the other hand, GC-FTIR demonstrated more distinguishable spectra. The spectra for the homologous compounds showed however, that the GC-FTIR technique was less successful compared to GC-MS. Also a pronounced fragmentation pattern for some of the cathinones was found.

    In conclusion, this thesis highlights the importance of using complementary techniques for the univocal identification of synthetic cannabinoids and cathinones. By increasing the number of analogues investigated, the more may be learnt about the capabilities of different techniques for structural differentiations, and thereby providing important identification criteria leading to trustworthy forensic evidence.

    List of papers
    1. Prediction of designer drugs: synthesis and spectroscopic analysis of synthetic cannabinoid analogues of 1H-indol-3-yl(2,2,3,3-tetramethylcyclopropyl) methanone and 1H-indol-3-yl(adamantan-1-yl)methanone
    Open this publication in new window or tab >>Prediction of designer drugs: synthesis and spectroscopic analysis of synthetic cannabinoid analogues of 1H-indol-3-yl(2,2,3,3-tetramethylcyclopropyl) methanone and 1H-indol-3-yl(adamantan-1-yl)methanone
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    2016 (English)In: Drug Testing and Analysis, ISSN 1942-7603, E-ISSN 1942-7611, Vol. 8, no 10, p. 1015-1029Article in journal (Refereed) Published
    Abstract [en]

    In this work, emergence patterns of synthetic cannabinoids were utilized in an attempt to predict those that may appear on the drug market in the future. Based on this information, two base structures of the synthetic cannabinoid analogues - (1H-indol-3-yl (2,2,3,3-tetramethylcyclopropyl) methanone and 1H-indol-3-yl(adamantan-1-yl)methanone) - together with three substituents butyl, 4-fluorobutyl and ethyl tetrahydropyran - were selected for synthesis. This resulted in a total of six synthetic cannabinoid analogues that to the authors knowledge have not yet appeared on the drug market. Spectroscopic data, including nuclearmagnetic resonance (NMR), mass spectrometry (MS), and Fourier transforminfrared (FTIR) spectroscopy (solid and gas phase), are presented for the synthesized analogues and some additional related cannabinoids. In this context, the suitability of the employed techniques for the identification of unknowns is discussed and the use of GC-FTIR as a secondary complementary technique to GC-MS is addressed. Examples of compounds that are difficult to differentiate by their mass spectra, but can be distinguished based upon their gas phase FTIR spectra are presented. Conversely, structural homologueswhere mass spectra aremore powerful than gas phase FTIR spectra for unambiguous assignments are also exemplified. This work further emphasizes that a combination of several techniques is the key to success in structural elucidations. Copyright (C) 2015 John Wiley amp; Sons, Ltd.

    Place, publisher, year, edition, pages
    WILEY-BLACKWELL, 2016
    Keywords
    drug analysis; proactive; synthetic cannabinoids; synthesis; mass spectrometry
    National Category
    Pharmaceutical Sciences
    Identifiers
    urn:nbn:se:liu:diva-132473 (URN)10.1002/dta.1904 (DOI)000384806400003 ()26526273 (PubMedID)
    Note

    Funding Agencies|Swedish Contingencies Agency (MSB)

    Available from: 2016-11-13 Created: 2016-11-12 Last updated: 2018-01-13
  • 63.
    Carlsson, Andreas
    et al.
    Swedish National Forens Centre NFC, SE-58194 Linkoping, Sweden.
    Lindberg, Sandra
    Swedish Def Research Agency, Sweden.
    Wu, Xiongyu
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Dunne, Simon
    Swedish National Forens Centre NFC, SE-58194 Linkoping, Sweden.
    Josefsson, Martin
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering. National Board Forens Med, Department Forens Genet and Forens Toxicol, SE-58758 Linkoping, Sweden.
    Astot, Crister
    Swedish Def Research Agency, Sweden.
    Dahlén, Johan
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Prediction of designer drugs: synthesis and spectroscopic analysis of synthetic cannabinoid analogues of 1H-indol-3-yl(2,2,3,3-tetramethylcyclopropyl) methanone and 1H-indol-3-yl(adamantan-1-yl)methanone2016In: Drug Testing and Analysis, ISSN 1942-7603, E-ISSN 1942-7611, Vol. 8, no 10, p. 1015-1029Article in journal (Refereed)
    Abstract [en]

    In this work, emergence patterns of synthetic cannabinoids were utilized in an attempt to predict those that may appear on the drug market in the future. Based on this information, two base structures of the synthetic cannabinoid analogues - (1H-indol-3-yl (2,2,3,3-tetramethylcyclopropyl) methanone and 1H-indol-3-yl(adamantan-1-yl)methanone) - together with three substituents butyl, 4-fluorobutyl and ethyl tetrahydropyran - were selected for synthesis. This resulted in a total of six synthetic cannabinoid analogues that to the authors knowledge have not yet appeared on the drug market. Spectroscopic data, including nuclearmagnetic resonance (NMR), mass spectrometry (MS), and Fourier transforminfrared (FTIR) spectroscopy (solid and gas phase), are presented for the synthesized analogues and some additional related cannabinoids. In this context, the suitability of the employed techniques for the identification of unknowns is discussed and the use of GC-FTIR as a secondary complementary technique to GC-MS is addressed. Examples of compounds that are difficult to differentiate by their mass spectra, but can be distinguished based upon their gas phase FTIR spectra are presented. Conversely, structural homologueswhere mass spectra aremore powerful than gas phase FTIR spectra for unambiguous assignments are also exemplified. This work further emphasizes that a combination of several techniques is the key to success in structural elucidations. Copyright (C) 2015 John Wiley amp; Sons, Ltd.

  • 64.
    Carlsson, Andreas
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering. Swedish Natl Forens Ctr NFC, SE-58194 Linkoping, Sweden.
    Sandgren, Veronica
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Svensson, Stefan
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Konradsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Dunne, Simon
    Swedish Natl Forens Ctr NFC, SE-58194 Linkoping, Sweden.
    Josefsson, Martin
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering. Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Dahlén, Johan
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Prediction of designer drugs: Synthesis and spectroscopic analysis of synthetic cathinone analogs that may appear on the Swedish drug market2018In: Drug Testing and Analysis, ISSN 1942-7603, E-ISSN 1942-7611, Vol. 10, no 7, p. 1076-1098Article in journal (Refereed)
    Abstract [en]

    The use of hyphenated analytical techniques in forensic drug screening enables simultaneous identification of a wide range of different compounds. However, the appearance of drug seizures containing new substances, mainly new psychoactive substances (NPS), is steadily increasing. These new and other already known substances often possess structural similarities and consequently they exhibit spectral data with slight differences. This situation has made the criteria that ensure indubitable identification of compounds increasingly important. In this work, 6 new synthetic cathinones that have not yet appeared in any Swedish drug seizures were synthesized. Their chemical structures were similar to those of already known cathinone analogs of which 42 were also included in the study. Hence, a total of 48 synthetic cathinones making up sets of homologous and regioisomeric compounds were used to challenge the capabilities of various analytical techniques commonly applied in forensic drug screening, ie, gas chromatography-mass spectrometry (GC-MS), gas chromatography-Fourier transform infrared spectroscopy (GC-FTIR), nuclear magnetic resonance (NMR), and liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). Special attention was paid to the capabilities of GC-MS and GC-FTIR to distinguish between the synthetic cathinones and the results showed that neither GC-MS nor GC-FTIR alone can successfully differentiate between all synthetic cathinones. However, the 2 techniques proved to be complementary and their combined use is therefore beneficial. For example, the structural homologs were better differentiated by GC-MS, while GC-FTIR performed better for the regioisomers. Further, new spectroscopic data of the synthesized cathinone analogs is hereby presented for the forensic community. The synthetic work also showed that cathinone reference compounds can be produced in few reaction steps.

  • 65.
    Chermá, Maria D.
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Josefsson, Martin
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Rydberg, Irene
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Woxler, Per
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Dependency in Linköping.
    Trygg, Tomas
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Dependency in Linköping.
    Hollertz, Olle
    Department of General Psychiatry, Västervik Hospital, Västervik, Sweden.
    Gustafsson, Per A.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Methylphenidate for Treating ADHD: A Naturalistic Clinical Study of Methylphenidate Blood Concentrations in Children and Adults With Optimized Dosage.2017In: European journal of drug metabolism and pharmacokinetics, ISSN 0378-7966, E-ISSN 2107-0180, Vol. 42, no 2, p. 295-307Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Methylphenidate (MPH), along with behavioral and psychosocial interventions, is the first-line medication to treat attention-deficit hyperactivity disorder (ADHD) in Sweden. The dose of MPH for good symptom control differs between patients. However, studies of MPH concentration measurement in ADHD treatment are limited.

    OBJECTIVE: To describe blood and oral fluid (OF) concentrations of MPH after administration of medication in patients with well-adjusted MPH treatment for ADHD, and to identify the most suitable matrix for accurate MPH concentration during treatment.

    METHODS: Patients were recruited from Child and Adolescent Psychiatry (CAP), General Psychiatry (GP), and the Department of Dependency (DD). Blood and OF samples were collected in the morning before MPH administration as well as 1 and 6 h after administration of the prescribed morning dose of MPH.

    RESULTS: Fifty-nine patients aged between 9 and 69 years, 76 % males. The daily dose of MPH varied from 18 to 180 mg, but the median daily dose per body weight was similar, approximately 1.0 mg/kg body weight. The median MPH concentration in blood 1 and 6 h after the morning dose was 5.4 and 9.3 ng/mL, respectively. Highly variable OF-to-blood ratios for MPH were found at all time points for all three groups.

    CONCLUSIONS: Weight is a reliable clinical parameter for optimal dose titration. Otherwise, MPH blood concentration might be used for individual dose optimization and for monitoring of the prescribed dose. Relying only on the outcome in OF cannot be recommended for evaluation of accurate MPH concentrations for treatment monitoring.

  • 66.
    Chey, Chan Oeurn
    et al.
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, The Institute of Technology.
    Patra, Hirak K
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, The Institute of Technology.
    Tengdelius, Mattias
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Golabi, Mohsen
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, The Institute of Technology.
    Parlak, Onur
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, The Institute of Technology.
    Imani, Roghayeh
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, The Institute of Technology.
    Elhag, Sami A. I.
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, The Institute of Technology.
    Yandi, Wetra
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics. Linköping University, The Institute of Technology.
    Tiwari, Ashutosh
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, The Institute of Technology.
    Impact of nanotoxicology towards technologists to end users2013In: Advanced Materials Letters, ISSN 0976-3961, E-ISSN 0976-397X, Vol. 4, no 8, p. 591-597Article in journal (Refereed)
    Abstract [en]

    The length scale for nanomaterial is small enough to be invisible and presume innocence for the initial avoidance of the toxicity issues. Again it was beyond the understanding of the time frame when nanotechnology just blooms that a length scale itself might be an important toxic parameter apart from its materialistic properties. We present this report to address the fundamental issues and questions related to the nanotoxicity issues from laboratory to the land of applications. We emphasize about the basic nanoscale materials that are regularly being used by the scientific community and the nanotechnology based materials that has already in the market or will come soon.

  • 67.
    Chirica, Laura C.
    et al.
    Department of Chemistry, Biochemistry, Umeå University, Umeå, Sweden.
    Petersson, Christoffer
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Hurtig, Marina
    Department of Odontology, Umeå University, Umeå, Sweden.
    Jonsson, Bengt-Harald
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Borén, Thomas
    Department of Odontology, Umeå University, Umeå, Sweden.
    Lindskog, Sven
    Department of Chemistry, Biochemistry, Umeå University, Umeå, Sweden.
    Expression and localization of α- and β-carbonic anhydrase in Helicobacter pylori2002In: Biochimica et Biophysica Acta - Proteins and Proteomics, ISSN 1570-9639, E-ISSN 1878-1454, Vol. 1601, no 2, p. 192-199Article in journal (Refereed)
    Abstract [en]

    Helicobacter pylori, the causative agent of peptic ulcer disease, expresses two different forms of the zinc-containing enzyme carbonic anhydrase (CA) (α and β), catalyzing the reversible hydration of CO2. Presumably, the high CO2 requirement of H. pylori implies an important role for this enzyme in the bacterial physiology. In this paper, expression of the CAs has been analyzed in three different strains of the bacterium, 26695, J99 and 17.1, and appears to be independent of CO2 concentration in the investigated range (0.1–10%). Presence of the potent and highly specific CA inhibitor, acetazolamide, in the medium does not seem to inhibit bacterial growth at the given sulfonamide concentration. Moreover, the localization and distribution of the α-CA was analyzed by immunonegative staining, while SDS-digested freeze-fracture immunogold labelling was used for the β-form of the enzyme. The latter method has the advantage of allowing assessment of protein localization to distinct cell compartments and membrane structures. The resulting electron microscopy images indicate a localization of the β-CA in the cytosol, on the cytosolic side of the inner membrane and on the outer membrane facing the periplasmic space. The α-enzyme was found attached to the surface of the bacterium.

  • 68.
    Choong, Ferdinand
    et al.
    Karolinska Institutet, Stockholm, Sweden.
    Bäck, Marcus
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Fahlen, Sara
    Karolinska Institutet, Stockholm, Sweden.
    Johansson, Leif B. G.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Melican, Keira
    Karolinska Institutet, Stockholm, Sweden.
    Rhen, Mikael
    Karolinska Institutet, Stockholm, Sweden.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Richter-Dahlfors, Agneta
    Karolinska Institutet, Stockholm, Sweden.
    Real-time opto-tracing of curli and cellulose in live Salmonella biofilms using conjugated oligothiophenes2016In: npj Biofilms and Microbiomes, ISSN 2055-5008, Vol. 2, article id 16024Article in journal (Refereed)
    Abstract [en]

    Extracellular matrix (ECM) is the protein- and polysaccharide-rich backbone of bacterial biofilms that provides a defensive barrier in clinical, environmental and industrial settings. Understanding the dynamics of biofilm formation in native environments has been hindered by a lack of research tools. Here we report a method for simultaneous, real-time, in situ detection and differentiation of the Salmonella ECM components curli and cellulose, using non-toxic, luminescent conjugated oligothiophenes (LCOs). These flexible conjugated polymers emit a conformation-dependent fluorescence spectrum, which we use to kinetically define extracellular appearance of curli fibres and cellulose polysaccharides during bacterial growth. The scope of this technique is demonstrated by defining biofilm morphotypes of Salmonella enterica serovars Enteritidis and Typhimurium, and their isogenic mutants in liquid culture and on solid media, and by visualising the ECM components in native biofilms. Our reported use of LCOs across a number of platforms, including intracellular cellulose production in eukaryotic cells and in infected tissues, demonstrates the versatility of this optotracing technology, and its ability to redefine biofilm research.

  • 69.
    Choong, Ferdinand X.
    et al.
    Karolinska Inst, Sweden.
    Bäck, Marcus
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Schulz, Anette
    Karolinska Inst, Sweden.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Edlund, Ulrica
    KTH Royal Inst Technol, Sweden.
    Richter-Dahlfors, Agneta
    Karolinska Inst, Sweden.
    Stereochemical identification of glucans by oligothiophenes enables cellulose anatomical mapping in plant tissues2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 3108Article in journal (Refereed)
    Abstract [en]

    Efficient use of plant-derived materials requires enabling technologies for non-disruptive composition analysis. The ability to identify and spatially locate polysaccharides in native plant tissues is difficult but essential. Here, we develop an optical method for cellulose identification using the structure-responsive, heptameric oligothiophene h-FTAA as molecular fluorophore. Spectrophotometric analysis of h-FTAA interacting with closely related glucans revealed an exceptional specificity for beta-linked glucans. This optical, non-disruptive method for stereochemical differentiation of glycosidic linkages was next used for in situ composition analysis in plants. Multi-laser/multi-detector analysis developed herein revealed spatial localization of cellulose and structural cell wall features such as plasmodesmata and perforated sieve plates of the phloem. Simultaneous imaging of intrinsically fluorescent components revealed the spatial relationship between cell walls and other organelles, such as chloroplasts and lignified annular thickenings of the trachea, with precision at the sub-cellular scale. Our non-destructive method for cellulose identification lays the foundation for the emergence of anatomical maps of the chemical constituents in plant tissues. This rapid and versatile method will likely benefit the plant science research fields and may serve the biorefinery industry as reporter for feedstock optimization as well as in-line monitoring of cellulose reactions during standard operations.

  • 70.
    Choong, Ferdinand X.
    et al.
    Karolinska Institute, Sweden.
    Bäck, Marcus
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Steiner, Svava E.
    Karolinska Institute, Sweden.
    Melican, Keira
    Karolinska Institute, Sweden.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Edlund, Ulrica
    KTH Royal Institute Technology, Sweden.
    Richter-Dahlfors, Agneta
    Karolinska Institute, Sweden.
    Nondestructive, real-time determination and visualization of cellulose, hemicellulose and lignin by luminescent oligothiophenes2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 35578Article in journal (Refereed)
    Abstract [en]

    Enabling technologies for efficient use of the bio-based feedstock are crucial to the replacement of oil-based products. We investigated the feasibility of luminescent conjugated oligothiophenes (LCOs) for non-destructive, rapid detection and quality assessment of lignocellulosic components in complex biomass matrices. A cationic pentameric oligothiophene denoted p-HTEA (pentamer hydrogen thiophene ethyl amine) showed unique binding affinities to cellulose, lignin, hemicelluloses, and cellulose nanofibrils in crystal, liquid and paper form. We exploited this finding using spectrofluorometric methods and fluorescence confocal laser scanning microscopy, for sensitive, simultaneous determination of the structural and compositional complexities of native lignocellulosic biomass. With exceptional photostability, p-HTEA is also demonstrated as a dynamic sensor for real-time monitoring of enzymatic cellulose degradation in cellulolysis. These results demonstrate the use of p-HTEA as a non-destructive tool for the determination of cellulose, hemicellulose and lignin in complex biomass matrices, thereby aiding in the optimization of biomass-converting technologies.

  • 71.
    Choong, Ferdinand X.
    et al.
    Karolinska Inst, Sweden.
    Lantz, Linda
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Shirani, Hamid
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Schulz, Anette
    Karolinska Inst, Sweden.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Edlund, Ulrica
    KTH Royal Inst Technol, Sweden.
    Richter-Dahlfors, Agneta
    Karolinska Inst, Sweden.
    Stereochemical identification of glucans by a donor-acceptor-donor conjugated pentamer enables multi-carbohydrate anatomical mapping in plant tissues2019In: Cellulose (London), ISSN 0969-0239, E-ISSN 1572-882X, Vol. 26, no 7, p. 4253-4264Article in journal (Refereed)
    Abstract [en]

    Optotracing is a novel method for analytical imaging of carbohydrates in plant and microbial tissues. This optical method applies structure-responsive oligothiophenes as molecular fluorophores emitting unique optical signatures when bound to polysaccharides. Herein, we apply Carbotrace680, a short length anionic oligothiophene with a central heterocyclic benzodithiazole (BTD) motif, to probe for different glucans. The donor-acceptor-donor type electronic structure of Carbotrace680 provides improved spectral properties compared to oligothiophenes due to the possibility of intramolecular charge-transfer transition to the BTD motif. This enables differentiation of glucans based on the glycosidic linkage stereochemistry. Thus -configured starch is readily differentiated from -configured cellulose. The versatility of optotracing is demonstrated by dynamic monitoring of thermo-induced starch remodelling, shown in parallel by spectrophotometry and microscopy of starch granules. Imaging of Carbotrace680 bound to multiple glucans in plant tissues provided direct identification of their physical locations, revealing the spatial relationship between structural (cellulose) and storage (starch) glucans at sub-cellular scale. Our work forms the basis for the development of superior optotracers for sensitive detection of polysaccharides. Our non-destructive method for anatomical mapping of glucans in biomass will serve as an enabling technology for developments towards efficient use of plant-derived materials and biomass. [GRAPHICS] .

  • 72.
    Chu, Tak-Ho
    et al.
    University of Calgary, Canada.
    Cummins, Karen
    University of Calgary, Canada.
    Sparling, Joseph S.
    University of Calgary, Canada.
    Tsutsui, Shigeki
    University of Calgary, Canada.
    Brideau, Craig
    University of Calgary, Canada.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Joseph, Jeffrey T.
    Alberta Health Serv, Canada.
    Stys, Peter K.
    University of Calgary, Canada.
    Axonal and myelinic pathology in 5xFAD Alzheimers mouse spinal cord2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 11, article id e0188218Article in journal (Refereed)
    Abstract [en]

    As an extension of the brain, the spinal cord has unique properties which could allow us to gain a better understanding of CNS pathology. The brain and cord share the same cellular components, yet the latter is simpler in cytoarchitecture and connectivity. In Alzheimers research, virtually all focus is on brain pathology, however it has been shown that transgenic Alzheimers mouse models accumulate beta amyloid plaques in spinal cord, suggesting that the cord possesses the same molecular machinery and conditions for plaque formation. Here we report a spatial-temporal map of plaque load in 5xFAD mouse spinal cord. We found that plaques started to appear at 11 weeks, then exhibited a time dependent increase and differential distribution along the cord. More plaques were found in cervical than other spinal levels at all time points examined. Despite heavy plaque load at 6 months, the number of cervical motor neurons in 5xFAD mice is comparable to wild type littermates. On detailed microscopic examination, fine beta amyloid-containing and beta sheet-rich thread-like structures were found in the peri-axonal space of many axons. Importantly, these novel structures appear before any plaque deposits are visible in young mice spinal cord and they co-localize with axonal swellings at later stages, suggesting that these thread-like structures might represent the initial stages of plaque formation, and could play a role in axonal damage. Additionally, we were able to demonstrate increasing myelinopathy in aged 5xFAD mouse spinal cord using the lipid probe Nile Red with high resolution. Collectively, we found significant amyloid pathology in grey and white matter of the 5xFAD mouse spinal cord which indicates that this structure maybe a useful platform to study mechanisms of Alzheimers pathology and disease progression.

  • 73.
    Chubarov, M.
    et al.
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology. Not Found: Linkoping Univ, Dept Phys Chem and Biol, SE-58183 Linkoping, Sweden .
    Pedersen, Henrik
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Högberg, Hans
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, The Institute of Technology.
    Czigany, Zs.
    Hungarian Academic Science, Hungary .
    Henry, Anne
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, The Institute of Technology.
    Chemical vapour deposition of epitaxial rhombohedral BN thin films on SiC substrates2014In: CrystEngComm, ISSN 1466-8033, E-ISSN 1466-8033, Vol. 16, no 24, p. 5430-5436Article in journal (Refereed)
    Abstract [en]

    Epitaxial growth of rhombohedral boron nitride (r-BN) on different polytypes of silicon carbide (SiC) is demonstrated using thermally activated hot-wall chemical vapour deposition and triethyl boron and ammonia as precursors. With respect to the crystalline quality of the r-BN films, we investigate the influence of the deposition temperature, the precursor ratio (N/B) and the addition of a minute amount of silicon to the gas mixture. From X-ray diffraction and transmission electron microscopy, we find that the optimal growth temperature for epitaxial r-BN on the Si-face of the SiC substrates is 1500 degrees C at a N/B ratio of 642 and silicon needs to be present not only in the gas mixture during deposition but also on the substrate surface. Such conditions result in the growth of films with a c-axis identical to that of the bulk material and a thickness of 200 nm, which is promising for the development of BN films for electronic applications.

  • 74.
    Chubarov, M.
    et al.
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Pedersen, Henrik
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Högberg, Hans
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, The Institute of Technology.
    Filippov, Stanislav
    Linköping University, Department of Physics, Chemistry and Biology, Functional Electronic Materials. Linköping University, The Institute of Technology.
    Engelbrecht, J.A. A.
    Nelson Mandela Metropolitan University, South Africa .
    O'Connel, J.
    Nelson Mandela Metropolitan University, South Africa .
    Henry, Anne
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, The Institute of Technology.
    Boron nitride: A new photonic material2014In: Physica. B, Condensed matter, ISSN 0921-4526, E-ISSN 1873-2135, Vol. 439, p. 29-34Article in journal (Refereed)
    Abstract [en]

    Rhombohedral boron nitride (r-BN) layers were grown on sapphire substrate in a hot-wall chemical vapor deposition reactor. Characterization of these layers is reported in details. X-ray diffraction (XRD) is used as a routine characterization tool to investigate the crystalline quality of the films and the identification of the phases is revealed using detailed pole figure measurements. Transmission electron microscopy reveals stacking of more than 40 atomic layers. Results from Fourier Transform InfraRed (FTIR) spectroscopy measurements are compared with XRD data showing that FTIR is not phase sensitive when various phases of sp(2)-BN are investigated. XRD measurements show a significant improvement of the crystalline quality when adding silicon to the gas mixture during the growth; this is further confirmed by cathodoluminescence which shows a decrease of the defects related luminescence intensity.

  • 75.
    Chubarov, M.
    et al.
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Pedersen, Henrik
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Högberg, Hans
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, The Institute of Technology.
    Filippov, Stanislav
    Linköping University, Department of Physics, Chemistry and Biology, Functional Electronic Materials. Linköping University, The Institute of Technology.
    Engelbrecht, J.A. A.
    Nelson Mandela Metropolitan University, Port Elizabeth, South Africa.
    O'Connel, J.
    Nelson Mandela Metropolitan University, Port Elizabeth, South Africa.
    Henry, Anne
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, The Institute of Technology.
    Characterization of Boron Nitride Thin Films2013Conference paper (Refereed)
    Abstract [en]

    Rhombohedral Boron Nitride layers were grown on sapphire substrate in a hot-wall CVD reactor. The characterization of those layers is reported and the results are discussed in correlation with the various growth parameters used.

  • 76.
    Chubarov, Mikhail
    et al.
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Science & Engineering.
    Högberg, Hans
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Henry, Anne
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Pedersen, Henrik
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Challenge in determining the crystal structure of epitaxial 0001 oriented sp(2)-BN films2018In: Journal of Vacuum Science & Technology. A. Vacuum, Surfaces, and Films, ISSN 0734-2101, E-ISSN 1520-8559, Vol. 36, no 3, article id 030801Article, review/survey (Refereed)
    Abstract [en]

    Boron nitride (BN) as a thin film is promising for many future electronic applications. On 0001 alpha-Al2O3 and 0001 4H/6H-SiC substrates, chemical vapor deposition yields epitaxial sp(2)-hybridized BN (sp(2)-BN) films oriented around the c-axis. Here, the authors seek to point out that sp(2)-BN can form two different polytypes; hexagonal BN (h-BN) and rhombohedral BN (r-BN), only differing in the stacking of the basal planes but with the identical distance between the basal planes and in-plane lattice parameters. This makes structural identification challenging in c- axis oriented films. The authors suggest the use of a combination of high-resolution electron microscopy with careful sample preparation and thin film x-ray diffraction techniques like pole figure measurements and glancing incidence (in-plane) diffraction to fully distinguish h-BN from r-BN. (C) 2018 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license.

  • 77.
    Chubarov, Mikhail
    et al.
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Pedersen, Henrik
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Högberg, Hans
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, The Institute of Technology.
    Czigany, Zsolt
    Hungarian Academic Science, Hungary .
    Andersson, Sven G.
    Linköping University, Department of Physics, Chemistry and Biology, Semiconductor Materials. Linköping University, The Institute of Technology.
    Henry, Anne
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, The Institute of Technology.
    Nucleation and initial growth of sp2-BNon α-Al2O3 and SiC by chemical vapour deposition2014Manuscript (preprint) (Other academic)
    Abstract [en]

    Knowledge on thin films evolution from the early stages of growth is important for the control of quality and properties of the film. Here we present study of the early growth stages and evolution of the crystalline structure of sp2 hybridised Boron Nitride (BN) thin films deposited by chemical vapour deposition from triethyl boron and ammonia. Nucleation of hexagonal BN (h-BN) is observed already at 1200 °C on α-Al2O3 substrate with an AlN buffer layer (AlN/α-Al2O3) while no formation of h-BN is detected when the growth is done on 6H-SiC in a growth temperature range between 1200 °C and 1700 °C. We demonstrate that h-BN grows on AlN/α-Al2O3 exhibiting a layer-by-layer growth mode up to ca. 4 nm followed by a transition to r-BN growth when grown at 1500 °C. The following r-BN growth is suggested to proceed with mixed layer-by-layer and island growth mode; after a thin continuous layer of r-BN, islands formation is favoured leading to a twinned r-BN structure of the film. We find that h-BN does not grow on 6H-SiC substrates instead r-BN nucleates and grows directly as a twinned crystal. The twinning is found to be suppressed by a surface preparation of the SiC substrate with SiH4 prior to BN growth. These results open up for a more controlled epitaxial growth of sp2-BN for future electronic applications.

  • 78.
    Chubarov, Mikhail
    et al.
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Pedersen, Henrik
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Högberg, Hans
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, The Institute of Technology.
    Czigany, Zsolt
    Hungarian Academic Science, Hungary .
    Garbrecht, Magnus
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, The Institute of Technology.
    Henry, Anne
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, The Institute of Technology.
    Polytype pure sp2-BN thin films as dictated by the substrate crystal structure2015In: Chemistry of Materials, ISSN 0897-4756, E-ISSN 1520-5002, Vol. 27, no 5, p. 1640-1645Article in journal (Refereed)
    Abstract [en]

    Boron nitride (BN) is a promising semiconductor material, but its current exploration is hampered by difficulties in growth of single crystalline phase-pure thin films. We compare the growth of sp2-BN by chemical vapor deposition on (0001) 6H-SiC and on (0001) α-Al2O3 substrates with an AlN buffer layer. Polytype-pure rhombohedral BN (r-BN) with a thickness of 200 nm is observed on SiC whereas hexagonal BN (h-BN) nucleates and grows on the AlN buffer layer. For the latter case after a thickness of 4 nm, the h-BN growth is followed by r-BN growth to a total thickness of 200 nm. We find that the polytype of the sp2-BN films is determined by the ordering of Si-C or Al-N atomic pairs in the underlying crystalline structure (SiC or AlN). In the latter case the change from h-BN to r-BN is triggered by stress relaxation. This is important for the development of BN semiconductor device technology.

  • 79.
    Chubarov, Mikhail
    et al.
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Science & Engineering.
    Pedersen, Henrik
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Högberg, Hans
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Henry, Anne
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Czigany, Zsolt
    Hungarian Academic Science, Hungary.
    Initial stages of growth and the influence of temperature during chemical vapor deposition of sp(2)-BN films2015In: Journal of Vacuum Science & Technology. A. Vacuum, Surfaces, and Films, ISSN 0734-2101, E-ISSN 1520-8559, Vol. 33, no 6, p. 061520-Article in journal (Refereed)
    Abstract [en]

    Knowledge of the structural evolution of thin films, starting by the initial stages of growth, is important to control the quality and properties of the film. The authors present a study on the initial stages of growth and the temperature influence on the structural evolution of sp(2) hybridized boron nitride (BN) thin films during chemical vapor deposition (CVD) with triethyl boron and ammonia as precursors. Nucleation of hexagonal BN (h-BN) occurs at 1200 degrees C on alpha-Al2O3 with an AlN buffer layer (AlN/alpha-Al2O3). At 1500 degrees C, h-BN grows with a layer-by-layer growth mode on AlN/alpha-Al2O3 up to similar to 4 nm after which the film structure changes to rhombohedral BN (r-BN). Then, r-BN growth proceeds with a mixed layer-by-layer and island growth mode. h-BN does not grow on 6H-SiC substrates; instead, r-BN nucleates and grows directly with a mixed layer-by-layer and island growth mode. These differences may be caused by differences in substrate surface temperature due to different thermal conductivities of the substrate materials. These results add to the understanding of the growth process of sp(2)-BN employing CVD. (C) 2015 American Vacuum Society.

  • 80.
    Cieslar-Pobuda, Artur
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Bäck, Marcus
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Magnusson, Karin
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Vilas Jain, Mayur
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Rafat, Mehrdad
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Health Sciences.
    Ghavami, Saeid
    Manitoba Institute Child Heatlh, Canada; University of Manitoba, Canada .
    Nilsson, Peter R.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Los, Marek Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Cell Type Related Differences in Staining with Pentameric Thiophene Derivatives2014In: Cytometry Part A, ISSN 1552-4922, E-ISSN 1552-4930, Vol. 85A, no 7, p. 628-635Article in journal (Refereed)
    Abstract [en]

    Fluorescent compounds capable of staining cells selectively without affecting their viability are gaining importance in biology and medicine. Recently, a new family of optical dyes, denoted luminescent conjugated oligothiophenes (LCOs), has emerged as an interesting class of highly emissive molecules for studying various biological phenomena. Properly functionalized LCOs have been utilized for selective identification of disease-associated protein aggregates and for selective detection of distinct cells. Herein, we present data on differential staining of various cell types, including cancer cells. The differential staining observed with newly developed pentameric LCOs is attributed to distinct side chain functionalities along the thiophene backbone. Employing flow cytometry and fluorescence microscopy we examined a library of LCOs for stainability of a variety of cell lines. Among tested dyes we found promising candidates that showed strong or moderate capability to stain cells to different extent, depending on target cells. Hence, LCOs with diverse imidazole motifs along the thiophene backbone were identified as an interesting class of agents for staining of cancer cells, whereas LCOs with other amino acid side chains along the backbone showed a complete lack of staining for the cells included in the study. Furthermore, for p-HTMI,a LCO functionalized with methylated imidazole moieties, the staining was dependent on the p53 status of the cells, indicating that the molecular target for the dye is a cellular component regulated by p53. We foresee that functionalized LCOs will serve as a new class of optical ligands for fluorescent classification of cells and expand the toolbox of reagents for fluorescent live imaging of different cells.

  • 81.
    Ciobanu, C V
    et al.
    Ohio State Univ, Dept Phys, Columbus, OH 43210 USA.
    Ojamäe, Lars
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Shavitt, I
    Ohio State Univ, Dept Phys, Columbus, OH 43210 USA.
    Singer, S J
    Ohio State Univ, Dept Phys, Columbus, OH 43210 USA.
    Structure and vibrational spectra of H(+)(H(2)O)(8): Is the excess proton in a symmetrical hydrogen bond?2000In: Journal of Chemical Physics, ISSN 0021-9606, E-ISSN 1089-7690, Vol. 113, no 13, p. 5321-5330, article id PII [S0021-9606(00)30735-8]Article in journal (Refereed)
    Abstract [en]

    The energetics, structure, and vibrational spectra of a wide variety of H + (H 2 O) 8 structures are calculated using density functional theory and second-order Møller–Plesset ab initio methods. In these isomers of H + (H 2 O) 8 the local environment of the excess proton sometimes resembles a symmetric H 5 O + 2 structure and sometimes H 3 O + , but many structures are intermediate between these two limits. We introduce a quantitative measure of the degree to which the excess proton resembles H 5 O + 2 or H 3 O + . Other bond lengths and, perhaps most useful, the position of certain vibrational bands track this measure of the symmetry in the local structure surrounding the excess proton. The general trend is for the most compact structures to have the lowest energy. However, adding zero-point energy counteracts this trend, making prediction of the most stable isomer impossible at this time. At elevated temperatures corresponding to recent experiments and atmospheric conditions (150–200 K), calculated Gibbs free energies clearly favor the least compact structures, in agreement with recent thermal simulations [Singer, McDonald, and Ojamäe, J. Chem. Phys. 112, 710 (2000)]. © 2000 American Institute of Physics.

  • 82.
    Civitelli, Livia
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Sandin, Linnea
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Nelson, Erin
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science.
    Iqbal Khattak, Sikander
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Brorsson, Ann-Christin
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Kågedal, Katarina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    The Luminescent Oligothiophene p-FTAA Converts Toxic A beta(1-42) Species into Nontoxic Amyloid Fibers with Altered Properties2016In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 291, no 17, p. 9233-9243Article in journal (Refereed)
    Abstract [en]

    Aggregation of the amyloid-(beta) peptide (A beta) in the brain leads to the formation of extracellular amyloid plaques, which is one of the pathological hallmarks of Alzheimer disease (AD). It is a general hypothesis that soluble prefibrillar assemblies of the A beta peptide, rather than mature amyloid fibrils, cause neuronal dysfunction and memory impairment in AD. Thus, reducing the level of these prefibrillar species by using molecules that can interfere with the A beta fibrillation pathway may be a valid approach to reduce A beta cytotoxicity. Luminescent-conjugated oligothiophenes (LCOs) have amyloid binding properties and spectral properties that differ when they bind to protein aggregates with different morphologies and can therefore be used to visualize protein aggregates. In this study, cell toxicity experiments and biophysical studies demonstrated that the LCO p-FTAA was able to reduce the pool of soluble toxic A beta species in favor of the formation of larger insoluble nontoxic amyloid fibrils, there by counteracting A beta-mediated cytotoxicity. Moreover, p-FTAA bound to early formed A beta species and induced a rapid formation of beta-sheet structures. These p-FTAA generated amyloid fibrils were less hydrophobic and more resistant to proteolysis by proteinase K. In summary, our data show that p-FTAA promoted the formation of insoluble and stable A beta species that were nontoxic which indicates that p-FTAA might have therapeutic potential.

  • 83.
    Csizmok, Veronika
    et al.
    Hospital Sick Children, Canada; University of British Columbia, Canada.
    Montecchio, Meri
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Science & Engineering.
    Lin, Hong
    Hospital Sick Children, Canada.
    Tyers, Mike
    University of Montreal, Canada.
    Sunnerhagen, Maria
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Forman-Kay, Julie D.
    Hospital Sick Children, Canada; University of Toronto, Canada.
    Multivalent Interactions with Fbw7 and Pin1 Facilitate Recognition of c-Jun by the SCFFbw7 Ubiquitin Ligase2018In: Structure, ISSN 0969-2126, E-ISSN 1878-4186, Vol. 26, no 1, p. 28-+Article in journal (Refereed)
    Abstract [en]

    Many regulatory proteins, including the transcription factor c-Jun, are highly enriched in disordered protein regions that govern growth, division, survival, differentiation, and response to signals. The stability of c-Jun is controlled by poorly understood regulatory interactions of its disordered region with both the E3 ubiquitin ligase SCFFbw7 and prolyl cis-trans isomerase Pin1. We use nuclear magnetic resonance and fluorescence studies of c-Jun to demonstrate that multisite c-Jun phosphorylation is required for high-affinity interaction with Fbw7. We show that the Pin1 WW and PPIase domains interact in a dynamic complex with multiply phosphorylated c-Jun. Importantly, Pin1 isomerizes a pSer-Pro peptide bond at the c-Jun N terminus that affects binding to Fbw7 and thus modulates the ubiquitin-mediated degradation of c-Jun. Our findings support the general principle that multiple weak binding motifs within disordered regions can synergize to yield high-affinity interactions and provide rapidly evolvable means to build and fine-tune regulatory events.

  • 84.
    Dahlgren, Anders
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Johansson, Per-Ola
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Kvarnström, Ingemar
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Musil, Djordje
    AstraZeneca R&D, Structural Chemistry Laboratory, Mölndal, Sweden.
    Nilsson, Ingemar
    AstraZeneca R&D, Medicinal Chemistry, Mölndal, Sweden.
    Samuelsson, Bertil
    Department of Organic Chemistry, Stockholm University, Stockholm, Sweden and Medivir AB, Huddinge, Sweden.
    Novel morpholinone-based D-Phe-Pro-Arg mimics as potential thrombin inhibitors: design, synthesis, and X-ray crystal structure of an enzyme inhibitor complex2002In: Bioorganic & Medicinal Chemistry, ISSN 0968-0896, E-ISSN 1464-3391, Vol. 10, no 6, p. 1829-1839Article in journal (Refereed)
    Abstract [en]

    A morpholinone structural motif derived from d(+)- and l(−)-malic acid has been used as a mimic of d-Phe-Pro in the thrombin inhibiting tripeptide d-Phe-Pro-Arg. In place of Arg the more rigid P1 truncated p-amidinobenzylamine (Pab) or 2-amino-5-aminomethyl-3-methyl-pyridine have been utilized. The synthetic strategy developed readily delivers these novel thrombin inhibitors used to probe the α-thrombin inhibitor binding site. The best candidate in this series of thrombin inhibitors exhibits an in vitro IC50 of 720 nM. The X-ray crystal structure of this candidate co-crystallized with α-thrombin is discussed.

  • 85.
    Danielsson, Örjan
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Semiconductor Materials. Linköping University, The Institute of Technology.
    Li, Xun
    Linköping University, Department of Physics, Chemistry and Biology, Semiconductor Materials. Linköping University, The Institute of Technology.
    Ojamäe, Lars
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Janzén, Erik
    Linköping University, Department of Physics, Chemistry and Biology, Semiconductor Materials. Linköping University, The Institute of Technology.
    Pedersen, Henrik
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Forsberg, Urban
    Linköping University, Department of Physics, Chemistry and Biology, Semiconductor Materials. Linköping University, Faculty of Science & Engineering.
    A model for carbon incorporation from trimethyl gallium in chemical vapor deposition of gallium nitride2016In: Journal of Materials Chemistry, ISSN 0959-9428, E-ISSN 1364-5501, Vol. 4, no 4, p. 863-871Article in journal (Refereed)
    Abstract [en]

    Gallium nitride (GaN) semiconductor material can become semi-insulating when doping with carbon. Semi-insulating buffer layers are utilized to prevent leakage currents in GaN high power devices. Carbon is inherently present during chemical vapor deposition (CVD) of GaN from the use of trimethyl gallium (TMGa) as precursor. TMGa decomposes in the gas phase, releasing its methyl groups, which could act as carbon source for doping. It is previously known that the carbon doping levels can be controlled by tuning the CVD process parameters, such as temperature, pressure and precursor flow rates. However, the mechanism for carbon incorporation from TMGa is not yet understood. In this paper, a model for predicting carbon incorporation from TMGa in GaN layers grown by CVD is proposed. The model is based on ab initio quantum chemical calculations of molecular adsorption and reaction energies. Using Computational Fluid Dynamics, with a chemical kinetic model for decomposition of the precursors and reactions in the gas phase, to calculate gas phase compositions at realistic process conditions, together with the proposed model, we obtain good correlations with measurements, for both carbon doping concentrations and growth rates, when varying the inlet NH3/TMGa ratio. When varying temperature (800 – 1050°C), the model overpredicts carbon doping concentrations at the lower temperatures, but predicts growth rates well, and the agreement with measured carbon doping concentrations is good above 1000°C.

  • 86.
    Darmastuti, Zhafira
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Bhattacharyya, P.
    Dept. of Electronics and Telecommunication Engineering, Bengal Engineering and Science University, India.
    Andersson, Mike
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Kanungo, Jayita
    IC Design & Fabrication Centre, Dept. of Electronics & Telecommunications Engineering, Jadavpur University, Kolkata, India.
    Basu, Sukumar
    IC Design & Fabrication Centre, Dept. of Electronics & Telecommunications Engineering, Jadavpur University, Kolkata, India.
    Käll, Per-Olov
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Inorganic Chemistry.
    Ojamäe, Lars
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Chemistry.
    Lloyd Spetz, Anita
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    SiC-FET methanol sensors for process control and leakage detection2013In: Sensors and actuators. B, Chemical, ISSN 0925-4005, E-ISSN 1873-3077, Vol. 187, no SI, p. 553-562Article in journal (Refereed)
    Abstract [en]

    Two types of SiC based field effect transistor sensors, with Pt or Ir gate, were tested to detect methanol in the concentration range of 0–1600 ppm for both process control and leak detection applications. The methanol response was investigated both with and without oxygen, since the process control might be considered as oxygen free application, while the sensor is operated in air during leak detection. Pt sensors offered very fast response with appreciably high response magnitude at 200 °C, while Ir sensors showed both higher response and response time up to 300 °C, but this decreased considerably at 350 °C. Cross sensitivity effect in presence of oxygen, hydrogen, propene and water vapor was also investigated. The presence of oxygen improved the response of both sensors, which is favorable for the leak detection application. Hydrogen had a large influence on the methanol response of both sensors, propene had a negligible influence, while water vapor changed direction of the methanol response for the Pt sensor. The detection mechanism and different sensing behavior of Pt and Ir gate sensors were discussed in the light of model reaction mechanisms derived from hybrid density-functional theory quantum-chemical calculations.

  • 87.
    Darmastuti, Zhafira
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Applied Sensor Science. Linköping University, The Institute of Technology.
    Bhattacharyya, Partha
    Bengal Engineering and Science University, India.
    Basu, Sukumar
    Jadavpur University, India.
    Käll, Per-Olov
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Ojamäe, Lars
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Lloyd Spetz, Anita
    Linköping University, Department of Physics, Chemistry and Biology, Applied Sensor Science. Linköping University, The Institute of Technology.
    SiC - FET Sensors for methanol leakage detection2012In: Proceeding of the 14th International Meeting on Chemical Sensors (IMCS 2012), 2012, p. 1579-1582Conference paper (Other academic)
    Abstract [en]

    Pt and Ir SiC based Field Effect Transistor sensors were tested to detect low concentration of methanol (<200 ppm) for both process control and leak detection applications. Pt sensors gave good and very fast response at 200°C, while Ir sensors gave larger but much slower response. The presence of oxygen improved the response of the sensor which was favorable for the leak detection application. The influence of hydrogen and propene to the sensor response was also studied. Beside the experimental work, the detection mechanism and different sensing behavior of Pt and Ir were studied by quantum chemical calculations.

  • 88.
    Darmastuti, Zhafira
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Applied Sensor Science. Linköping University, The Institute of Technology.
    Bounechada, Djamela
    Competence Centre for Catalysis / Dept. of Chemical and Biological Engineering, Chalmers University of Technology, Göteborg, Sweden.
    Carlsson, P-A
    Competence Centre for Catalysis / Dept. of Chemical and Biological Engineering, Chalmers University of Technology, Göteborg, Sweden.
    Lindqvist, N.
    Alstom Power AB, Växjö, Sweden.
    Andersson, Mike
    Linköping University, Department of Physics, Chemistry and Biology, Applied Sensor Science. Linköping University, The Institute of Technology.
    Skoglundh, Magnus
    Competence Centre for Catalysis / Dept. of Chemical and Biological Engineering, Chalmers University of Technology, Göteborg, Sweden.
    Carlsson, P-A
    Competence Centre for Catalysis /Dept. of Chemical and Biological Engineering, Chalmers University of Technology, Göteborg, Sweden.
    Lloyd Spetz, Anita
    Linköping University, Department of Physics, Chemistry and Biology, Applied Sensor Science. Linköping University, The Institute of Technology.
    Ojamae, Lars
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Detection mechanism studies of SO2 on Pt / SiO2 systemManuscript (preprint) (Other academic)
    Abstract [en]

    Experiment was performed with Pt-gate SiC-FET sensors to study the detection mechanism of the sensors. The sensing measurement showed that oxygen influenced the response quite strongly. The sensor response became larger in the presence of oxygen. Experiment with mass spectroscopy indicated the formation of SO3 during the sensing measurement. Further experiment with DRIFT spectroscopy showed the formation of sulfate species on the oxide surface, accompanied by the disappearance of the silanol groups. An explanatory model was built based on quantum-chemical calculations. The results strengthened the experimental results by showing that it was more energetically favorable for SO2 to oxidize into SO3 before being adsorbed on the oxide surface. It was also observed that the overall adsorption reaction was exothermic, the activation energy for the SO2 oxidation was 48,75 kJ/mol, and the rate limiting step was the desorption of SO3 from the Pt surface.

  • 89.
    Darmastuti, Zhafira
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Applied Sensor Science. Linköping University, The Institute of Technology.
    Ojamäe, Lars
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Chemistry.
    Andersson, Mike
    Linköping University, Department of Physics, Chemistry and Biology, Applied Sensor Science. Linköping University, The Institute of Technology.
    Lloyd Spetz, Anita
    Linköping University, Department of Physics, Chemistry and Biology, Applied Sensor Science. Linköping University, The Institute of Technology.
    SiC-FET as SO2 Sensors - Detection Mechanism Studies2014In: Proc IMCS 2014, Buenos Aires, Argentine, March 17-19, MPS-T3-4, 2014Conference paper (Refereed)
  • 90.
    Deminskyi, Petro
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Rouf, Polla
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Ivanov, Ivan Gueorguiev
    Linköping University, Department of Physics, Chemistry and Biology, Semiconductor Materials. Linköping University, Faculty of Science & Engineering.
    Pedersen, Henrik
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Atomic layer deposition of InN using trimethylindium and ammonia plasma2019In: Journal of Vacuum Science & Technology. A. Vacuum, Surfaces, and Films, ISSN 0734-2101, E-ISSN 1520-8559, Vol. 37, no 2, article id 020926Article in journal (Refereed)
    Abstract [en]

    Indium nitride (InN) is a low bandgap, high electron mobility semiconductor material of interest to optoelectronics and telecommunication. Such applications require the deposition of uniform crystalline InN thin films on large area substrates, with deposition temperatures compatible with this temperature-sensitive material. As conventional chemical vapor deposition (CVD) struggles with the low temperature tolerated by the InN crystal, the authors hypothesize that a time-resolved, surface-controlled CVD route could offer a way forward for InN thin film deposition. In this work, the authors report atomic layer deposition of crystalline, wurtzite InN thin films using trimethylindium and ammonia plasma on Si(100). They found a narrow atomic layer deposition window of 240-260 degrees C with a deposition rate of 0.36 A/cycle and that the flow of ammonia into the plasma is an important parameter for the crystalline quality of the film. X-ray diffraction measurements further confirmed the polycrystalline nature of InN thin films. X-ray photoelectron spectroscopy measurements show nearly stoichiometric InN with low carbon level (amp;lt;1 at. %) and oxygen level (amp;lt;5 at. %) in the film bulk. The low carbon level is attributed to a favorable surface chemistry enabled by the NH3 plasma. The film bulk oxygen content is attributed to oxidation upon exposure to air via grain boundary diffusion and possibly by formation of oxygen containing species in the plasma discharge. Published by the AVS.

  • 91.
    D'Ercole, A
    et al.
    Unita INFM Torino, I-10125 Turin, Italy.
    Giamello, E
    Unita INFM Torino, I-10125 Turin, Italy.
    Pisani, C
    Unita INFM Torino, I-10125 Turin, Italy.
    Ojamäe, Lars
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Embedded-cluster study of hydrogen interaction with an oxygen vacancy at the magnesium oxide surface1999In: JOURNAL OF PHYSICAL CHEMISTRY B, ISSN 1089-5647, Vol. 103, no 19, p. 3872-3876Article in journal (Refereed)
    Abstract [en]

    An embedded-cluster Hartree−Fock approximation is adopted for simulating the formation of Fs(H) color centers at the (001) surface of magnesium oxide. This process is assumed to take place in two steps at an isolated surface anion vacancy:  first, a hydrogen molecule is adsorbed dissociatively at the defect; second, following UV irradiation, a neutral hydrogen atom is removed and an electron remains trapped at the vacancy with a hydroxyl group nearby. According to the present calculations, the activation energy for the dissociation is appreciable (about 25 kcal/mol) and the products (a proton bound to a low-coordinated oxygen and a hydride ion above the vacancy) are considerably less stable than the reactants. The excitation of the adsorbed species owing to the UV irradiation is simulated by considering a singlet−triplet transition of the hydride−vacancy complex, which then dissociates into an H atom and a trapped lone electron. The electronic structure and the EPR parameters of the resulting paramagnetic state are explored. The theoretical results agree in many respects with the experimental data as concerns one of the forms of heterolitically dissociated hydrogen which are found at the defective MgO surface. However, from the viewpoint of the energetics, this model is untenable because that species is known to form irreversibly at room temperature with low activation energy.

  • 92.
    Domert, Jakob
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Rao, Sahana Bhima
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Agholme, Lotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Brorsson, Ann-Christin
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Nath, Sangeeta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Spreading of Amyloid-β Peptides via Neuritic Cell-to-cell Transfer Is Dependent on Insufficient Cellular Clearance2014In: Neurobiology of Disease, ISSN 0969-9961, E-ISSN 1095-953X, Vol. 65, p. 82-92Article in journal (Refereed)
    Abstract [en]

    The spreading of pathology through neuronal pathways is likely to be the cause of the progressive cognitive loss observed in Alzheimer's disease (AD) and other neurodegenerative diseases. We have recently shown the propagation of AD pathology via cell-to-cell transfer of oligomeric amyloid beta (Aβ) residues 1-42 (oAβ1-42) using our donor-acceptor 3-D co-culture model. We now show that different Aβ-isoforms (fluorescently labeled 1-42, 3(pE)-40, 1-40 and 11-42 oligomers) can transfer from one cell to another. Thus, transfer is not restricted to a specific Aβ-isoform. Although different Aβ isoforms can transfer, differences in the capacity to clear and/or degrade these aggregated isoforms result in vast differences in the net amounts ending up in the receiving cells and the net remaining Aβ can cause seeding and pathology in the receiving cells. This insufficient clearance and/or degradation by cells creates sizable intracellular accumulations of the aggregation-prone Aβ1-42 isoform, which further promotes cell-to-cell transfer; thus, oAβ1-42 is a potentially toxic isoform. Furthermore, cell-to-cell transfer is shown to be an early event that is seemingly independent of later appearances of cellular toxicity. This phenomenon could explain how seeds for the AD pathology could pass on to new brain areas and gradually induce AD pathology, even before the first cell starts to deteriorate, and how cell-to-cell transfer can act together with the factors that influence cellular clearance and/or degradation in the development of AD.

  • 93.
    Dovega, Rebecca
    et al.
    Karolinska Institutet, Stockholm, Sweden.
    Tsutakawa, Susan
    Lawrence Berkeley National Lab (LBNL), Berkeley, California, USA.
    Quistgaard, Esben M.
    Karolinska Institutet, Stockholm, Sweden.
    Anandapadmanaban, Madhanagopal
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology. Karolinska Institutet, Stockholm, Sweden.
    Löw, Christian
    Karolinska Institutet, Stockholm, Sweden.
    Nordlund, Pär
    Karolinska Institutet, Stockholm, Sweden; Nanyang Technology University, Singapore .
    Structural and Biochemical Characterization of Human PR70 in Isolation and in Complex with the Scaffolding Subunit of Protein Phosphatase 2A2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 7, p. e0101846-Article in journal (Refereed)
    Abstract [en]

    Protein Phosphatase 2A (PP2A) is a major Ser/Thr phosphatase involved in the regulation of various cellular processes. PP2A assembles into diverse trimeric holoenzymes, which consist of a scaffolding (A) subunit, a catalytic (C) subunit and various regulatory (B) subunits. Here we report a 2.0 angstrom crystal structure of the free B /PR70 subunit and a SAXS model of an A/PR70 complex. The crystal structure of B /PR70 reveals a two domain elongated structure with two Ca2+ binding EF-hands. Furthermore, we have characterized the interaction of both binding partner and their calcium dependency using biophysical techniques. Ca2+ biophysical studies with Circular Dichroism showed that the two EF-hands display different affinities to Ca2+. In the absence of the catalytic C-subunit, the scaffolding A-subunit remains highly mobile and flexible even in the presence of the B /PR70 subunit as judged by SAXS. Isothermal Titration Calorimetry studies and SAXS data support that PR70 and the A-subunit have high affinity to each other. This study provides additional knowledge about the structural basis for the function of B containing holoenzymes.

  • 94.
    Ekeroth, Johan
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Konradsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Organic Chemistry. Linköping University, The Institute of Technology.
    Björefors, Fredrik
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics. Linköping University, The Institute of Technology.
    Lundström, Ingemar
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Liedberg, Bo
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics. Linköping University, The Institute of Technology.
    Monitoring the interfacial capacitance at self-assembled phosphate monolayers on gold electrodes upon interaction with calcium and magnesium2002In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 74, no 9, p. 1979-1985Article in journal (Refereed)
    Abstract [en]

    Electrochemical impedance spectroscopy has been used to evaluate the change in interracial capacitance upon calcium and magnesium coordination to a phosphate-modified electrode. The phosphate electrode was prepared via immobilization of phosphorylated, thiol-containing, serine analogues onto gold. Upon subjection to calcium and magnesium, a substantial drop in capacitance was observed. Magnesium displayed the largest influence on the capacitance: a 27% capacitance drop was observed upon introduction of a 1 mM solution of magnesium ions. The lowered capacitance is a result of a change in the potential and charge distribution at the film/electrolyte interface as the cations coordinate to the phosphate groups. Moreover, the relationship between electrode potential and capacitance has been investigated and reveals a significant difference between monovalent and divalent cations. As complementary information, infrared reflection absorption spectra of the phosphorylated monolayer having different counterions are presented. The results reported in this paper indicate that the phosphorylated amino acid analogue monolayers could be used in investigations of the biochemically important coordination of calcium and magnesium to phosphates and phosphorylated amino acids.

  • 95.
    Elgland, Mathias
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Synthesis and application of β-configured [18/19F]FDGs: Novel prosthetic CuAAC click chemistry fluoroglycosylation tools for amyloid PET imaging and cancer theranostics2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Positron emission tomography (PET) is a non-invasive imaging method that renders three-dimensional images of tissue that selectively has taken up a radiolabelled organic compound, referred to as a radiotracer. This excellent technique provides clinicians with a tool to monitor disease progression and to evaluate how the patient respond to treatment. The by far most widely employed radiotracer in PET is called 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG), which is often referred to as the golden standard in PET. From a molecular perspective, [18F]FDG is an analogue of glucose where a hydroxyl group has been replaced with a radioactive fluorine atom (18F). It is well known that covalent attachment of carbohydrates (i.e., glycosylation) to biomolecules tend to improve their properties in the body, in terms of; improved pharmacokinetics, increased metabolic stability and faster clearance from blood and other non-specific tissue. It is therefore natural to pursuit the development of a [18F]fluoroglycosylation method where [18F]FDG is chemically conjugated to a ligand with high affinity for a given biological target (e.g., tumors or disease-associated protein aggregates).

    This thesis describes a novel [18F]fluoroglycosylation method that in a simple and general manner facilitate the conjugation of [18F]FDG to biological ligands using click chemistry. The utility of the developed [18F]fluoroglycosylation method is demonstrated by radiolabelling of curcumin, thus forming a tracer that may be employed for diagnosis of Alzheimer’s disease. Moreover, a set of oligothiophenes were fluoroglycosylated for potential diagnosis of Alzheimer’s disease but also for other much rarer protein misfolding diseases (e.g., Creutzfeldt-Jakob disease and systemic amyloidosis). In addition, the synthesis of a series of 19F-fluoroglycosylated porphyrins is described which exhibited promising properties not only to detect but also to treat melanoma cancer. Lastly, the synthesis of a set of 19F-fluorinated E-stilbenes, structurally based on the antioxidant resveratrol is presented. The E-stilbenes were evaluated for their capacity to spectrally distinguish between native and protofibrillar transthyretin in the pursuit of finding diagnostic markers for the rare but severe disease, transthyretin amyloidosis.

    List of papers
    1. beta-Configured clickable [F-18] FDGs as novel F-18-fluoroglycosylation tools for PET
    Open this publication in new window or tab >>beta-Configured clickable [F-18] FDGs as novel F-18-fluoroglycosylation tools for PET
    Show others...
    2017 (English)In: New Journal of Chemistry, ISSN 1144-0546, E-ISSN 1369-9261, Vol. 41, no 18, p. 10231-10236Article in journal (Refereed) Published
    Abstract [en]

    In oncology and neurology the F-18-radiolabeled glucose analogue 2-deoxy-2-[F-18]fluoro-D-glucose ([F-18]FDG) is by far the most commonly employed metabolic imaging agent for positron emission tomography (PET). Herein, we report a novel synthetic route to beta-configured mannopyranoside precursors and a chemoselective F-18-fluoroglycosylation method that employ two b-configured [F-18]FDG derivatives equipped with either a terminal azide or alkyne aglycon respectively, for use as a CuAAC clickable tool set for PET. The b-configured precursors provided the corresponding [F-18]FDGs in a radiochemical yield of 77-88%. Further, the clickability of these [F-18]FDGs was investigated by click coupling to the suitably functionalized Fmoc-protected amino acids, Fmoc-N-(propargyl)-glycine and Fmoc-3-azido-L-alanine, which provided the F-18-fluoroglycosylated amino acid conjugates in radiochemical yields of 75-83%. The F-18-fluoroglycosylated amino acids presented herein constitute a new and interesting class of metabolic PET radiotracers.

    Place, publisher, year, edition, pages
    ROYAL SOC CHEMISTRY, 2017
    National Category
    Organic Chemistry
    Identifiers
    urn:nbn:se:liu:diva-141934 (URN)10.1039/c7nj00716g (DOI)000411767400073 ()
    Note

    Funding Agencies|Swedish Foundation for Strategic Research; Swedish Research Council

    Available from: 2017-10-13 Created: 2017-10-13 Last updated: 2018-02-21
    2. Novel Trans-Stilbene-based Fluorophores as Probes for Spectral Discrimination of Native and Protofibrillar Transthyretin
    Open this publication in new window or tab >>Novel Trans-Stilbene-based Fluorophores as Probes for Spectral Discrimination of Native and Protofibrillar Transthyretin
    Show others...
    2016 (English)In: ACS Chemical Neuroscience, ISSN 1948-7193, E-ISSN 1948-7193, Vol. 7, no 7, p. 924-940Article in journal (Refereed) Published
    Abstract [en]

    Accumulation of misfolded transthyretin (TTR) as amyloid fibrils causes various human disorders. Native transthyretin is a neurotrophic protein and is a putative extracellular molecular chaperone. Several fluorophores have been shown in vitro to bind selectively to native TTR. Other compounds, such as thioflavin T, bind TTR amyloid fibrils. The probe 1-anilinonaphthalene-8-sulfonate (ANS) binds to both native and fibrillar TTR, becoming highly fluorescent, but with indistinguishable emission spectra for native and fibrillar TTR. Herein we report our efforts to develop a fluorescent small molecule capable of binding both native and misfolded protofibrillar TTR, providing distinguishable emission spectra. We used microwave synthesis for efficient production of a small library of trans-stilbenes and fluorescence spectral screening of their binding properties. We synthesized and tested 22 trans-stilbenes displaying a variety of functional groups. We successfully developed two naphthyl-based trans-stilbenes probes that detect both TTR states at physiological concentrations. The compounds bound with nanomolar to micromolar affinities and displayed distinct emission maxima upon binding native or misfolded protofibrillar TTR (>100 nm difference). The probes were mainly responsive to environment polarity providing evidence for the divergent hydrophobic structure of the binding sites of these protein conformational states. Furthermore, we were able to successfully use one of these probes to quantify the relative amounts of native and protofibrillar TTR in a dynamic equilibrium. In conclusion, we identified two trans-stilbene-based fluorescent probes, (E)-4-(2-(naphthalen-1-yl)vinyl)benzene-1,2-diol (11) and (E)-4-(2-(naphthalen-2-yl)vinyl)benzene-1,2-diol (14), that bind native and protofibrillar TTR, providing a wide difference in emission maxima allowing conformational discrimination by fluorescence spectroscopy. We expect these novel molecules to serve as important chemical biology research tools in studies of TTR folding and misfolding.

    Place, publisher, year, edition, pages
    American Chemical Society (ACS), 2016
    Keywords
    transthyretin, amyloid, stilbene, fluorescence, probe, spectrum
    National Category
    Chemical Sciences
    Identifiers
    urn:nbn:se:liu:diva-122842 (URN)10.1021/acschemneuro.6b00062 (DOI)000380297500009 ()27144293 (PubMedID)
    Note

    At the time for thesis presentation publication was in status: Manuscript

    Funding agencies:The work was supported by Goran Gustafsson's Foundation (PH), The Swedish Research Council (PH), The Linkoping center for systemic neuroscience, LiU-Neuro, (XW), and Sven and Lilly Lawski's foundation (ME).

    Available from: 2015-11-26 Created: 2015-11-26 Last updated: 2018-04-25Bibliographically approved
  • 96.
    Elgland, Mathias
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Nordeman, P.
    Uppsala University, Sweden.
    Fyrner, Timmy
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Antoni, G.
    Uppsala University, Sweden.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Konradsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    beta-Configured clickable [F-18] FDGs as novel F-18-fluoroglycosylation tools for PET2017In: New Journal of Chemistry, ISSN 1144-0546, E-ISSN 1369-9261, Vol. 41, no 18, p. 10231-10236Article in journal (Refereed)
    Abstract [en]

    In oncology and neurology the F-18-radiolabeled glucose analogue 2-deoxy-2-[F-18]fluoro-D-glucose ([F-18]FDG) is by far the most commonly employed metabolic imaging agent for positron emission tomography (PET). Herein, we report a novel synthetic route to beta-configured mannopyranoside precursors and a chemoselective F-18-fluoroglycosylation method that employ two b-configured [F-18]FDG derivatives equipped with either a terminal azide or alkyne aglycon respectively, for use as a CuAAC clickable tool set for PET. The b-configured precursors provided the corresponding [F-18]FDGs in a radiochemical yield of 77-88%. Further, the clickability of these [F-18]FDGs was investigated by click coupling to the suitably functionalized Fmoc-protected amino acids, Fmoc-N-(propargyl)-glycine and Fmoc-3-azido-L-alanine, which provided the F-18-fluoroglycosylated amino acid conjugates in radiochemical yields of 75-83%. The F-18-fluoroglycosylated amino acids presented herein constitute a new and interesting class of metabolic PET radiotracers.

  • 97.
    Ellingsen, Pal Gunnar
    et al.
    Norwegian University of Science and Technology, Norway .
    Nyström, Sofie
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Reitan, Nina Kristine
    Norwegian University of Science and Technology, Norway .
    Lindgren, Mikael
    Norwegian University of Science and Technology, Norway .
    Spectral correlation analysis of Amyloid beta plaque inhomogeneity from double staining experiments2013In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 18, no 10Article in journal (Refereed)
    Abstract [en]

    A spectral correlation algorithm for the analysis of hyperspectral fluorescence images is proposed by Ellingsen et al. [J. Biomed. Opt. 18, 020501 (2013)]. Here, it is applied to the analysis of double-stained A beta amyloid plaques being related to the Alzheimers disease (AD). Sections of APP/PS1 AD mice model brains are double stained with luminescent-conjugated oligothiophenes, known to bind to amyloid protein deposits. Hyperspectral fluorescence images of the brain sections are recorded and by applying the correlation algorithm the spectral inhomogeneity of the double-stained samples is mapped in terms of radial distribution and spectral content. To further investigate the progression of A beta amyloid plaque formation, 19 AD mice of different ages up to 23 months are characterized, enabling a statistical analysis of the plaque heterogeneity. In accordance with recent findings by Nystrom et al. [ACS Chem. Biol. 8, 1128-1133 (2013)], the spectral distribution within A beta plaques is found to vary with age throughout the lifespan of the mouse. With the new correlation algorithm, it is possible to quantify the spectral abundance of the two stains depending on the relative distance from the plaque center and mouse age. Thus, we demonstrate the use of the correlation analysis approach in double-staining experiments and how it is possible to relate these to structural/spectral changes in biological samples. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

  • 98.
    Enander, Karin
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Folded polypeptide scaffolds for biosensor and biochip applications: design, synthesis, functionalisation and characterisation2003Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis describes the design, synthesis and evaluation of functional molecular units intended for use in biosensor and microarray applications. A flexible, synthetic helix-loop-helix polypeptide that dimerises to form four-helix bundles was used as a scaffold and was modified with affinity ligands and fluorescent probes to specifically bind a target biomolecule and report on this event in an integrated process. The well-characterised binding of carbonic anhydrase by its benzenesulphonamide inhibitor was employed as a model interaction, and the emission intensity of the probe(s) was found to correlate with carbonic anhydrase concentration. A molecular array, spanning two orders of magnitude in affmity and useful for one-step target quantification, was designed by varying the spacer of the benzenesulphonamide derivative. The scaffold itself was found to contribute to binding, expanding the parameters available for affmity modulation. In a separate study focused on the interaction model system, it was revealed that a destabilising point mutation distant from the carbonic anhydrase active site resulted in faster dissociation rates of the benzenesulphonamide ligand. and that this effect was mediated by increased molecular dynamics caused by destabilisation.

    The fluorescence intensity difference displayed by free and target-bound peptides was found to be critically dependent on the position of the probe(s) in the scaffold, showing that the polypeptide fold, providing directionality of incorporated moieties, contributed considerably to peptide function. Dual labelling of the scaffold with different probes in positions where they displayed increased intensity in the corresponding single-probe peptides resulted in a synergistic emission increase upon target protein binding, significantly enhancing sensitivity. The peptides were shown to bind the target protein as monomers, and the molecular basis for sensing was a combination of specific peptide-protein interactions and dimer dissociation. The photochemical crosstalk between the probes was interrupted upon expulsion of one of the monomers upon binding.

    Strategies for thiol-dependent attachment of the peptides to modified gold surfaces were explored, and folding of immobilised scaffolds was demonstrated in the case of a model system with controllable dirnerisation properties. Results indicating that the sensing ability was retained upon peptide immobilisation were encouraging and prompted future studies on the relation between peptide structure and function, aiming at successful sensor surface and rnicroarray designs for the identification, quantification and characterisation of a wide variety of target biomolecules.

    List of papers
    1. Subtle differences in dissociation rates of interactions between destabilized human carbonic anhydrase II mutants and immobilized benzenesulfonamide inhibitors probed by a surface plasmon resonance biosensor
    Open this publication in new window or tab >>Subtle differences in dissociation rates of interactions between destabilized human carbonic anhydrase II mutants and immobilized benzenesulfonamide inhibitors probed by a surface plasmon resonance biosensor
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    2001 (English)In: Analytical Biochemistry, ISSN 0003-2697, E-ISSN 1096-0309, Vol. 296, no 2, p. 188-196Article in journal (Refereed) Published
    Abstract [en]

    The development of commercial biosensors based on surface plasmon resonance has made possible careful characterization of biomolecular interactions. Here, a set of destabilized human carbonic anhydrase II (HCA II) mutants was investigated with respect to their interaction kinetics with two different immobilized benzenesulfonamide inhibitors. Point mutations were located distantly from the active site, and the destabilization energies were up to 23 kJ/mol. The dissociation rate of wild-type HCA II, as determined from the binding to the inhibitor with higher affinity, was 0.019 s−1. For the mutants, dissociation rates were faster (0.022–0.025 s−1), and a correlation between faster dissociation and a high degree of destabilization was observed. We interpreted these results in terms of increased dynamics of the tertiary structures of the mutants. This interpretation was supported by entropy determinations, showing that the entropy of the native structure significantly increased upon destabilization of the protein molecule. Our findings demonstrate the applicability of modern biosensor technology in the study of subtle details in molecular interaction mechanisms, such as the long-range effect of point mutations on interaction kinetics.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-25364 (URN)10.1006/abio.2001.5301 (DOI)9807 (Local ID)9807 (Archive number)9807 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13
    2. Designed, folded polypeptide scaffolds that combine key biosensing events of recognition and reporting
    Open this publication in new window or tab >>Designed, folded polypeptide scaffolds that combine key biosensing events of recognition and reporting
    Show others...
    2002 (English)In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 67, no 9, p. 3120-3123Article in journal (Refereed) Published
    Abstract [en]

    No abstract available.

    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:liu:diva-42053 (URN)10.1021/jo010954n (DOI)59995 (Local ID)59995 (Archive number)59995 (OAI)
    Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
    3. A versatile polypeptide platform for integrated recognition and reporting: affinity arrays for protein-ligand interaction analysis
    Open this publication in new window or tab >>A versatile polypeptide platform for integrated recognition and reporting: affinity arrays for protein-ligand interaction analysis
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    2004 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 10, no 10, p. 2375-2385Article in journal (Refereed) Published
    Abstract [en]

    A molecular platform for protein detection and quantification is reported in which recognition has been integrated with direct monitoring of target-protein binding. The platform is based on a versatile 42-residue helix–loop–helix polypeptide that dimerizes to form four-helix bundles and allows site-selective modification with recognition and reporter elements on the side chains of individually addressable lysine residues. The well-characterized interaction between the model target-protein carbonic anhydrase and its inhibitor benzenesulfonamide was used for a proof-of-concept demonstration. An affinity array was designed where benzenesulfonamide derivatives with aliphatic or oligoglycine spacers and a fluorescent dansyl reporter group were introduced into the scaffold. The affinities of the array members for human carbonic anhydrase II (HCAII) were determined by titration with the target protein and were found to be highly affected by the properties of the spacers (dissociation constant Kd=0.02–3 μM). The affinity of HCAII for acetazolamide (Kd=4 nM) was determined in a competition experiment with one of the benzenesulfonamide array members to address the possibility of screening substance libraries for new target-protein binders. Also, successful affinity discrimination between different carbonic anhydrase isozymes highlighted the possibility of performing future isoform-expression profiling. Our platform is predicted to become a flexible tool for a variety of biosensor and protein-microarray applications within biochemistry, diagnostics and pharmaceutical chemistry.

    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:liu:diva-42052 (URN)10.1002/chem.200305391 (DOI)59994 (Local ID)59994 (Archive number)59994 (OAI)
    Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
    4. Designed, functionalized helix-loop-helix motifs that bind human carbonic anhydrase II: a new class of synthetic receptor molecules
    Open this publication in new window or tab >>Designed, functionalized helix-loop-helix motifs that bind human carbonic anhydrase II: a new class of synthetic receptor molecules
    2004 (English)In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 126, no 14, p. 4464-4465Article in journal (Refereed) Published
    Abstract [en]

    Polypeptides designed to fold into helix−loop−helix motifs and to dimerize to form four-helix bundles were functionalized by the introduction of a sulfonamide derivative known to bind human carbonic anhydrase II (HCAII) and one or both of the dansyl- and methoxycoumarin fluorescent probes. The 42-residue sequence DC that carries all three substituents in solvent-exposed positions was found to bind HCAII with a dissociation constant of 5 nM in aqueous solution at pH 7. At 2 μM concentration, DC was mainly dimeric in aqueous solution but bound HCAII as a monomer. Upon addition of a large excess of a helix−loop−helix motif without a high-affinity ligand, KE2-Q, a ternary complex was formed between HCAII, DC, and KE2-Q. Hydrophobic interactions between DC and HCAII and coordination of the sulfonamide group to the zinc ion of HCAII contributed cooperatively to binding in a demonstration of the usefulness of folded polypeptide−small organic molecule chimera as novel protein receptors. The DC homodimer was found to be a very sensitive biosensor component due to intermolecular quenching of its fluorescence that was inhibited upon binding to HCAII.

    National Category
    Engineering and Technology
    Identifiers
    urn:nbn:se:liu:diva-45770 (URN)10.1021/ja038799c (DOI)
    Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13
    5. Alpha-helix-inducing dimerization of synthetic polypeptide scaffolds on gold
    Open this publication in new window or tab >>Alpha-helix-inducing dimerization of synthetic polypeptide scaffolds on gold
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    2005 (English)In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 21, no 6, p. 2480-2487Article in journal (Refereed) Published
    Abstract [en]

    Designed, synthetic polypeptides that assemble into four-helix bundles upon dimerization in solution were studied with respect to folding on planar gold surfaces. A model system with controllable dimerization properties was employed, consisting of negatively and positively charged peptides. Circular dichroism spectroscopy and surface plasmon resonance based measurements showed that at neutral pH, the peptides were able to form heterodimers in solution, but unfavorable electrostatic interactions prevented the formation of homodimers. The dimerization propensity was found to be both pH- and buffer-dependent. A series of infrared absorption−reflection spectroscopy experiments of the polypeptides attached to planar gold surfaces revealed that if the negatively charged peptide was immobilized from a loading solution where it was folded, its structure was retained on the surface provided it had a cysteine residue available for anchoring to gold. If it was immobilized as random coil, it remained unstructured on the surface but was able to fold through heterodimerization if subsequently exposed to a positively charged polypeptide. When the positively charged peptide was immobilized as random coil, heterodimerization could not be induced, probably because of high-affinity interactions between the charged primary amine groups and the gold surface. These observations are intended to pave the way for future engineering of functional surfaces based on polypeptide scaffolds where folding is known to be crucial for function.

    Place, publisher, year, edition, pages
    ACS Publications, 2005
    National Category
    Other Basic Medicine
    Identifiers
    urn:nbn:se:liu:diva-15115 (URN)10.1021/la048029u (DOI)
    Available from: 2008-10-16 Created: 2008-10-16 Last updated: 2018-01-12Bibliographically approved
  • 99.
    Enander, Karin
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Dolphin, Gunnar
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Andersson, Linda
    Department of Organic Chemistry Göteborg University.
    Liedberg, Bo
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Lundström, Ingemar
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Baltzer, Lars
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Designed, folded polypeptide scaffolds that combine key biosensing events of recognition and reporting2002In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 67, no 9, p. 3120-3123Article in journal (Refereed)
    Abstract [en]

    No abstract available.

  • 100.
    Enander, Karin
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Dolphin, Gunnar
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Baltzer, Lars
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Designed, functionalized helix-loop-helix motifs that bind human carbonic anhydrase II: a new class of synthetic receptor molecules2004In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 126, no 14, p. 4464-4465Article in journal (Refereed)
    Abstract [en]

    Polypeptides designed to fold into helix−loop−helix motifs and to dimerize to form four-helix bundles were functionalized by the introduction of a sulfonamide derivative known to bind human carbonic anhydrase II (HCAII) and one or both of the dansyl- and methoxycoumarin fluorescent probes. The 42-residue sequence DC that carries all three substituents in solvent-exposed positions was found to bind HCAII with a dissociation constant of 5 nM in aqueous solution at pH 7. At 2 μM concentration, DC was mainly dimeric in aqueous solution but bound HCAII as a monomer. Upon addition of a large excess of a helix−loop−helix motif without a high-affinity ligand, KE2-Q, a ternary complex was formed between HCAII, DC, and KE2-Q. Hydrophobic interactions between DC and HCAII and coordination of the sulfonamide group to the zinc ion of HCAII contributed cooperatively to binding in a demonstration of the usefulness of folded polypeptide−small organic molecule chimera as novel protein receptors. The DC homodimer was found to be a very sensitive biosensor component due to intermolecular quenching of its fluorescence that was inhibited upon binding to HCAII.