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Binding of Polythiophenes to Amyloids: Structural Mapping of the Pharmacophore
Swiss Fed Inst Technol, Switzerland.
Univ Zurich, Switzerland.
Swiss Fed Inst Technol, Switzerland.
Univ Zurich, Switzerland.
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2018 (Engelska)Ingår i: ACS Chemical Neuroscience, ISSN 1948-7193, E-ISSN 1948-7193, Vol. 9, nr 3, s. 475-481Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Luminescent conjugated polythiophenes bind to amyloid proteins with high affinity. Their fluorescence properties, which are modulated by the detailed conformation in the bound state, are highly sensitive to structural features of the amyloid. Polythiophenes therefore represent diagnostic markers for the detection and differentiation of pathological amyloid aggregates. 560 We clarify the binding site and mode of two different polythiophenes to fibrils of the prion domain of the HET-s protein by solid-state NMR and correlate these findings with their fluorescence properties. We demonstrate how amyloid dyes recognize distinct binding sites with specific topological features. Regularly spaced surface charge patterns and well-accessible grooves on the fibril surface define the pharmacophore of the amyloid, which in turn determines the binding mode and fluorescence wavelength of the polythiophene.

Ort, förlag, år, upplaga, sidor
American Chemical Society (ACS), 2018. Vol. 9, nr 3, s. 475-481
Nyckelord [en]
Amyloid; pharmacophore; luminescent conjugated polythiophenes; diagnostic marker; fluorescence; solid-state NMR
Nationell ämneskategori
Biokemi och molekylärbiologi
Identifikatorer
URN: urn:nbn:se:liu:diva-147430DOI: 10.1021/acschemneuro.7b00397ISI: 000428356500012PubMedID: 29178774Scopus ID: 2-s2.0-85037681655OAI: oai:DiVA.org:liu-147430DiVA, id: diva2:1206545
Anmärkning

Funding Agencies|Swiss National Science Foundation [200020_159707, 200020_146757, 200020_147660]; French ANR [ANR-14-CE09-0024B]; European Research Council [ERC: 670958]

Tillgänglig från: 2018-05-17 Skapad: 2018-05-17 Senast uppdaterad: 2018-05-22Bibliografiskt granskad

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Hammarström, Per

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