Chemistry

Conformational analysis of thioflavin T bound to the surface of amyloid fibrils

Document Type

Article

Abstract

The interaction of small molecules with the surface of amyloid assemblies is important for the detection and inhibition of amyloid formation. Thioflavin T (ThT), a small molecular rotor, has been used for the detection of amyloid fibrils for over half a century. The basis for detection is simple in that in the presence of fibrils the fluorescence of ThT is dramatically enhanced. The mechanism for this enhancement is not well understood but may depend on the determination of the conformation of ThT bound to the fibril surface. Here, we first use solution-state 1H NMR to show that the on-off binding of ThT to the surface of insulin amyloid fibrils correlates with the enhancement of ThT fluorescence. We then show that the conformation of surface-bound ThT is twisted. The implications of this result in light of recent experimental and computational studies of the binding of ThT to amyloid or amyloid-like assemblies are discussed. © 2012 American Chemical Society.

Publication Title

Langmuir

Publication Date

12-4-2012

Volume

28

Issue

48

First Page

16490

Last Page

16495

ISSN

0743-7463

DOI

10.1021/la303677t

Cross Post Location

Student Publications

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