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Elgland, Mathias
Publications (4 of 4) Show all publications
Elgland, M. (2018). Synthesis and application of β-configured [18/19F]FDGs: Novel prosthetic CuAAC click chemistry fluoroglycosylation tools for amyloid PET imaging and cancer theranostics. (Doctoral dissertation). Linköping: Linköping University Electronic Press
Open this publication in new window or tab >>Synthesis and application of β-configured [18/19F]FDGs: Novel prosthetic CuAAC click chemistry fluoroglycosylation tools for amyloid PET imaging and cancer theranostics
2018 (English)Doctoral 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.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2018. p. 100
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1900
Keywords
FDG, clickable, PET, synthesis, in vivo imaging, theranostics
National Category
Organic Chemistry
Identifiers
urn:nbn:se:liu:diva-144323 (URN)10.3384/diss.diva-144323 (DOI)9789176853764 (ISBN)
Public defence
2018-03-23, Planck, Fysikhuset, Campus Valla, Linköping, 09:15 (English)
Opponent
Supervisors
Available from: 2018-02-15 Created: 2018-01-15 Last updated: 2019-09-30Bibliographically 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
Stavrinidou, E., Gabrielsson, R., Nilsson, K. P., Singh, S. K., Franco- Gonzalez, J. F., Volkov, A. V., . . . Berggren, M. (2017). In vivo polymerization and manufacturing of wires and supercapacitors in plants. Proceedings of the National Academy of Sciences of the United States of America, 114(11), 2807-2812
Open this publication in new window or tab >>In vivo polymerization and manufacturing of wires and supercapacitors in plants
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2017 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 114, no 11, p. 2807-2812Article in journal (Refereed) Published
Abstract [en]

Electronic plants, e-Plants, are an organic bioelectronic platform that allows electronic interfacing with plants. Recently we have demonstrated plants with augmented electronic functionality. Using the vascular system and organs of a plant, we manufactured organic electronic devices and circuits in vivo, leveraging the internal structure and physiology of the plant as the template, and an integral part of the devices. However, this electronic functionality was only achieved in localized regions, whereas new electronic materials that could be distributed to every part of the plant would provide versatility in device and circuit fabrication and create possibilities for new device concepts. Here we report the synthesis of such a conjugated oligomer that can be distributed and form longer oligomers and polymer in every part of the xylem vascular tissue of a Rosa floribunda cutting, forming long-range conducting wires. The plant’s structure acts as a physical template, whereas the plant’s biochemical response mechanism acts as the catalyst for polymerization. In addition, the oligomer can cross through the veins and enter the apoplastic space in the leaves. Finally, using the plant’s natural architecture we manufacture supercapacitors along the stem. Our results are preludes to autonomous energy systems integrated within plants and distribute interconnected sensor-actuator systems for plant control and optimization

Place, publisher, year, edition, pages
National Academy of Sciences, 2017
National Category
Plant Biotechnology Condensed Matter Physics Textile, Rubber and Polymeric Materials Chemical Sciences
Identifiers
urn:nbn:se:liu:diva-135492 (URN)10.1073/pnas.1616456114 (DOI)000396094200029 ()
Note

Funding agencies: Knut and Alice Wallenberg Foundation Scholar Grant [KAW 2012.0302]; Linkoping University; Onnesjo Foundation; Wenner-Gren Foundations; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkping University [SFO-Mat-

Available from: 2017-03-16 Created: 2017-03-16 Last updated: 2017-11-29Bibliographically approved
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
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