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Konradsson, Peter
Publications (10 of 70) Show all publications
Silverå Ejneby, M., Wu, X., Ottosson, N., Münger, E. P., Lundström, I., Konradsson, P. & Elinder, F. (2018). Atom-by-atom tuning of the electrostatic potassium-channel modulator dehydroabietic acid. The Journal of General Physiology, 150(5), 731-750
Open this publication in new window or tab >>Atom-by-atom tuning of the electrostatic potassium-channel modulator dehydroabietic acid
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2018 (English)In: The Journal of General Physiology, ISSN 0022-1295, E-ISSN 1540-7748, Vol. 150, no 5, p. 731-750Article in journal (Refereed) Published
Abstract [en]

Dehydroabietic acid (DHAA) is a naturally occurring component of pine resin that was recently shown to open voltage-gated potassium (KV) channels. The hydrophobic part of DHAA anchors the compound near the channel’s positively charged voltage sensor in a pocket between the channel and the lipid membrane. The negatively charged carboxyl group exerts an electrostatic effect on the channel’s voltage sensor, leading to the channel opening. In this study, we show that the channel-opening effect increases as the length of the carboxyl-group stalk is extended until a critical length of three atoms is reached. Longer stalks render the compounds noneffective. This critical distance is consistent with a simple electrostatic model in which the charge location depends on the stalk length. By combining an effective anchor with the optimal stalk length, we create a compound that opens the human KV7.2/7.3 (M type) potassium channel at a concentration of 1 µM. These results suggest that a stalk between the anchor and the effector group is a powerful way of increasing the potency of a channel-opening drug.

Place, publisher, year, edition, pages
New York, United States: Rockefeller Institute for Medical Research, 2018
National Category
Physiology
Identifiers
urn:nbn:se:liu:diva-147837 (URN)10.1085/jgp.201711965 (DOI)2-s2.0-85046705149 (Scopus ID)
Available from: 2018-05-15 Created: 2018-05-15 Last updated: 2018-06-04Bibliographically approved
Elgland, M., Nordeman, P., Fyrner, T., Antoni, G., Nilsson, P. & Konradsson, P. (2017). beta-Configured clickable [F-18] FDGs as novel F-18-fluoroglycosylation tools for PET. New Journal of Chemistry, 41(18), 10231-10236
Open this publication in new window or tab >>beta-Configured clickable [F-18] FDGs as novel F-18-fluoroglycosylation tools for PET
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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
Campos Melo, R. I., Wu, X., Elgland, M., Konradsson, P. & Hammarström, P. (2016). Novel Trans-Stilbene-based Fluorophores as Probes for Spectral Discrimination of Native and Protofibrillar Transthyretin. ACS Chemical Neuroscience, 7(7), 924-940
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
Ottosson, N., Wu, X., Nolting, A., Karlsson, U., Lund, P.-E., Ruda, K., . . . Elinder, F. (2015). Resin-acid derivatives as potent electrostatic openers of voltage-gated K channels and suppressors of neuronal excitability. Scientific Reports, 5(13278)
Open this publication in new window or tab >>Resin-acid derivatives as potent electrostatic openers of voltage-gated K channels and suppressors of neuronal excitability
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2015 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, no 13278Article in journal (Refereed) Published
Abstract [en]

Voltage-gated ion channels generate cellular excitability, cause diseases when mutated, and act as drug targets in hyperexcitability diseases, such as epilepsy, cardiac arrhythmia and pain. Unfortunately, many patients do not satisfactorily respond to the present-day drugs. We found that the naturally occurring resin acid dehydroabietic acid (DHAA) is a potent opener of a voltage-gated K channel and thereby a potential suppressor of cellular excitability. DHAA acts via a non-traditional mechanism, by electrostatically activating the voltage-sensor domain, rather than directly targeting the ion-conducting pore domain. By systematic iterative modifications of DHAA we synthesized 71 derivatives and found 32 compounds more potent than DHAA. The most potent compound, Compound 77, is 240 times more efficient than DHAA in opening a K channel. This and other potent compounds reduced excitability in dorsal root ganglion neurons, suggesting that resin-acid derivatives can become the first members of a new family of drugs with the potential for treatment of hyperexcitability diseases.

Place, publisher, year, edition, pages
Nature Publishing Group: Open Access Journals - Option C / Nature Publishing Group, 2015
National Category
Clinical Medicine Chemical Sciences
Identifiers
urn:nbn:se:liu:diva-121307 (URN)10.1038/srep13278 (DOI)000359905300001 ()26299574 (PubMedID)
Note

Funding Agencies|Swedish Research Council; Swedish Brain Foundation; Swedish Heart-Lung Foundation; ALF; County Council of Ostergotland

Available from: 2015-09-16 Created: 2015-09-14 Last updated: 2018-01-25Bibliographically approved
Tengdelius, M., Gurav, D., Konradsson, P., Påhlsson, P., Griffith, M. & Oommen, O. P. (2015). Synthesis and anticancer properties of fucoidan-mimetic glycopolymer coated gold nanoparticles. Chemical Communications, 51(40), 8532-8535
Open this publication in new window or tab >>Synthesis and anticancer properties of fucoidan-mimetic glycopolymer coated gold nanoparticles
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2015 (English)In: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 51, no 40, p. 8532-8535Article in journal (Refereed) Published
Abstract [en]

Gold nanoparticles coated with fucoidan-mimetic glycopolymers were synthesized that displayed good colloidal stability and promising anti-cancer properties. Fucoidan mimetic glycopolymers on their own were nontoxic, while glycopolymer coated gold nanoparticles displayed selective cytotoxicity to human colon cancer cell lines (HCT116) while it was non-toxic to mouse fibroblast cells (NIH3T3).

Place, publisher, year, edition, pages
ROYAL SOC CHEMISTRY, 2015
National Category
Chemical Sciences Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-119269 (URN)10.1039/c5cc02387d (DOI)000354043200034 ()25892661 (PubMedID)
Note

Funding Agencies|Swedish Strategic Research StemTherapy

Available from: 2015-06-12 Created: 2015-06-12 Last updated: 2017-12-04
Persson, K. M., Gabrielsson, R., Sawatdee, A., Nilsson, D., Konradsson, P. & Berggren, M. (2014). Electronic control over detachment of a self-doped water-soluble conjugated polyelectrolyte. Langmuir, 30(21), 6257-6266
Open this publication in new window or tab >>Electronic control over detachment of a self-doped water-soluble conjugated polyelectrolyte
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2014 (English)In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 30, no 21, p. 6257-6266Article in journal (Refereed) Published
Abstract [en]

Water-soluble conducting polymers are of interest to enable more versatile processing in aqueous media as well as to facilitate interactions with biomolecules. Here, we report a substituted poly(3,4-ethylenedioxythiophene) derivative (PEDOT-S:H) that is fully water-soluble and selfdoped. When electrochemically oxidizing a PEDOT-S:H thin film, the film detaches from the under-laying electrode. The oxidation of PEDOT-S:H starts with an initial phase of swelling followed by cracking before it finally disrupts and detaches from the electrode. We investigated the detachment mechanism and found that parameters such as the size, charge and concentration of ions in the electrolyte, the temperature and also the pH influence the characteristics of detachment. When oxidizing PEDOT-S:H, the positively charged polymer backbone is balanced by anions from the electrolyte solution and also by the sulphonate groups on the side chains (more self-doping). From our experiments, we conclude that detachment of the PEDOT-S:H film upon oxidation occurs in part due to swelling caused by an inflow of solvated anions and associated water, and in part due to rearrangements and strain within the film, caused by more self-doping. We believe that PEDOT-S:H detachment can be of interest in a number of different applications, including addressed and active control of the release of materials such as biomolecules and cell cultures.

Place, publisher, year, edition, pages
American Chemical Society, 2014
National Category
Polymer Chemistry Cell Biology
Identifiers
urn:nbn:se:liu:diva-106251 (URN)10.1021/la500693d (DOI)000336952800031 ()
Available from: 2014-04-30 Created: 2014-04-30 Last updated: 2017-12-05Bibliographically approved
Tengdelius, M., Lee, C.-J., Grenegård, M., Griffith, M., Påhlsson, P. & Konradsson, P. (2014). Synthesis and biological evaluation of fucoidan-mimetic glycopolymers through cyanoxyl-mediated free-radical polymerization. Biomacromolecules, 15(7), 2359-2368
Open this publication in new window or tab >>Synthesis and biological evaluation of fucoidan-mimetic glycopolymers through cyanoxyl-mediated free-radical polymerization
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2014 (English)In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 15, no 7, p. 2359-2368Article in journal (Refereed) Published
Abstract [en]

The sulfated marine polysaccharide fucoidan has been reported to have health benefits ranging from antivirus and anticancer properties to modulation of high blood pressure. Hence, they could enhance the biological function of materials for biomedical applications. However, the incorporation of fucoidan into biomaterials has been difficult, possibly due to its complex structure and lack of suitable functional groups for covalent anchoring to biomaterials. We have developed an approach for a rapid synthesis of fucoidanmimetic glycopolymer chains through cyanoxyl-mediated free-radical polymerization, a method suitable for chain-end functionalizing and subsequent linkage to biomaterials. The resulting sulfated and nonsulfated methacrylamido alpha-L-fucoside glycopolymers fucoidan-mimetic properties were studied in HSV-1 infection and platelet activation assays. The sulfated glycopolymer showed similar properties to natural fucoidan in inducing platelet activation and inhibiting HSV-1 binding and entry to cells, thus indicating successful syntheses of fucoidan-mimetic glycopolymers.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2014
National Category
Chemical Sciences Clinical Medicine Physical Sciences
Identifiers
urn:nbn:se:liu:diva-109382 (URN)10.1021/bm5002312 (DOI)000339090500003 ()24813544 (PubMedID)
Available from: 2014-08-15 Created: 2014-08-15 Last updated: 2017-12-05Bibliographically approved
Ericsson, E. M., Bui, L., Lundström, I., Konradsson, P., Liedberg, B. & Enander, K. (2013). Controlled orientation and covalent attachment of proteins on biosensor surfaces by Chelation Assisted Photoimmobilization. In: : . Paper presented at 3rd International Conference in Bio-Sensing Technology, 12-15 May 2013, Sitges, Spain.
Open this publication in new window or tab >>Controlled orientation and covalent attachment of proteins on biosensor surfaces by Chelation Assisted Photoimmobilization
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2013 (English)Conference paper, Oral presentation with published abstract (Other academic)
Abstract [en]

In the context of surface chemistry for affinity biosensor chips, it is widely accepted that uniform orientation of the immobilized recognition element (ligand) is preferred over random orientation. However, this assumption has often been based on studies where differences in ligand immobilization level have not been taken into account. In this contribution, we present a novel two-step method for homogenous orientation and covalent attachment of proteins to sensing surfaces, called Chelation Assisted Photoimmobilization (CAP). Careful quantification of the effect of ligand orientation on analyte responses was performed by comparing this strategy to immobilization by conventional amine coupling.

 In CAP, the chelation agent is nitrilotriacetic acid (NTA) which chelates Ni2+. A His-tagged ligand forms an oriented assembly when binding Ni2+-NTA and is then covalently bound to the surface via photolabile benzophenone (BP), which attacks C-H bonds upon UV light activation. We relied on a surface chemistry based on self-assembled monolayers (SAMs) of oligo(ethylene glycol) (OEG)-containing alkanethiolates on gold. Alkanethiols terminated with either NTA, BP or OEG were synthesized and mixed SAMs were characterized by infrared reflection absorption spectroscopy (IRAS), ellipsometry and contact angle goniometry. IRAS was also used to quantify ligand immobilization levels obtained either by CAP or by amine coupling via the carboxyl groups of an NTA-presenting surface. The model ligand was human IgG-Fc modified with a C-terminal 6xHis-tag and the analyte was Protein A. The ligand-analyte interaction was quantified by a surface plasmon resonance biosensor.

 Analyte responses were normalized with respect to the ligand amounts obtained by the two immobilization strategies. Interestingly, the normalized analyte response with randomly oriented ligand was >2 times higher than that with ligand immobilized by CAP. This shows that oriented ligand immobilization is not necessarily a means of increasing the sensitivity of a biosensor. Factors that may influence performance include the valency of the ligand and constraints related to the surface chemistry used for orientation.

National Category
Engineering and Technology
Identifiers
urn:nbn:se:liu:diva-108207 (URN)
Conference
3rd International Conference in Bio-Sensing Technology, 12-15 May 2013, Sitges, Spain
Available from: 2014-06-26 Created: 2014-06-26 Last updated: 2014-08-21
Ericsson, E., Enander, K., Bui, L., Lundström, I., Konradsson, P. & Liedberg, B. (2013). Controlled Orientation and Covalent Attachment of Proteins on Biosensor Surfaces by Chelation Assisted Photoimmobilization.
Open this publication in new window or tab >>Controlled Orientation and Covalent Attachment of Proteins on Biosensor Surfaces by Chelation Assisted Photoimmobilization
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2013 (English)Manuscript (preprint) (Other academic)
Abstract [en]

This report presents a novel method for uniform orientation and covalent attachment of proteins to sensing surfaces, termed Chelation Assisted Photoimmobilization (CAP). Alkanethiols terminated with either nitrilotriacetic acid (NTA), benzophenone (BP) or oligo(ethylene glycol) were synthesized and mixed self-assembled monolayers (SAMs) were prepared on gold and thoroughly characterized by infrared reflection absorption spectroscopy (IRAS), ellipsometry and contact angle goniometry. In the process of CAP, NTA chelates Ni2+ and the complex coordinates a His-tagged ligand in an oriented assembly. The ligand is then photoimmobilized via BP, which forms covalent bonds upon UV light activation. The CAP concept was demonstrated using human IgG-Fc modified with C-terminal hexahistidine tags (His-IgGFc) as the ligand and protein A as the analyte.

In the development of affinity biosensors, uniform orientation of ligand molecules where all analyte binding sites are accessible is often preferred to random orientation. In order to monitor the effect of ligand orientation on analyte response, the ligand-analyte interaction was quantified by surface plasmon resonance analysis, both in the case of CAP and when the ligand was attached by conventional amine coupling on surfaces presenting NTA. Responses were adjusted for differences in ligand immobilization level using IRAS. The normalized analyte response with randomly oriented ligand was 2.5 times higher than that with ligand immobilized by CAP, probably due to molecular crowding effects on the surface and the fact that His-IgGFc is bivalent for protein A. This is a reminder that many other factors than orientation alone may play a decisive role in analyte binding on biosensor surfaces.

Keywords
Biosensor, Surface chemistry, Protein immobilization, Orientation
National Category
Engineering and Technology
Identifiers
urn:nbn:se:liu:diva-87929 (URN)
Available from: 2013-01-29 Created: 2013-01-28 Last updated: 2013-01-31
Arja, K., Sjölander, D., Åslund, A., Prokop, S., Heppner, F. L., Konradsson, P., . . . Nilsson, P. (2013). Enhanced Fluorescent Assignment of Protein Aggregates by an Oligothiophene-Porphyrin-Based Amyloid Ligand. Macromolecular rapid communications, 34(9), 723-730
Open this publication in new window or tab >>Enhanced Fluorescent Assignment of Protein Aggregates by an Oligothiophene-Porphyrin-Based Amyloid Ligand
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2013 (English)In: Macromolecular rapid communications, ISSN 1022-1336, E-ISSN 1521-3927, Vol. 34, no 9, p. 723-730Article in journal (Refereed) Published
Abstract [en]

Fluorescent probes identifying protein aggregates are of great interest, as deposition of aggregated proteins is associated with many devastating diseases. Here, we report that a fluorescent amyloid ligand composed of two distinct molecular moieties, an amyloidophilic pentameric oligothiophene and a porphyrin, can be utilized for spectral and lifetime imaging assessment of recombinant A 1-42 amyloid fibrils and A deposits in brain tissue sections from a transgenic mouse model with Alzheimers disease pathology. The enhanced spectral range and distinct lifetime diversity of this novel oligothiopheneporphyrin-based ligand allow a more precise assessment of heterogeneous amyloid morphology compared with the corresponding oligothiophene dye.

Place, publisher, year, edition, pages
Wiley-VCH Verlag, 2013
Keywords
oligothiophene, porphyrin, protein deposits, imaging, fluorescence
National Category
Engineering and Technology
Identifiers
urn:nbn:se:liu:diva-93385 (URN)10.1002/marc.201200817 (DOI)000318354500004 ()
Note

Funding Agencies|Swedish Research Council||Knut and Alice Wallenberg Foundation||Swedish Foundation for Strategic Research||European Union FP7 HEALTH (Project LUPAS)||LiU Neuroscience Center||ERC Starting Independent Researcher grant (Project: MUMID)||

Available from: 2013-05-31 Created: 2013-05-31 Last updated: 2018-04-25
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