Incorporation of an azobenzene β-turn peptidomimetic into amyloid-β to probe potential structural motifs leading to β-sheet self-assembly

Todd M. Doran, Bradley L. Nilsson

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Alzheimer’s disease (AD) is characterized by chronic neurodegeneration and the insidious accumulation of senile plaques comprised of the amyloid-β (Aβ) peptide. An important goal in AD research is to characterize the structural basis for how Aβ aggregates exert their noxious effects on neurons. We describe herein synthetic steps to incorporate a light-controlled β-turn mimetic, 3-(3-aminomethylphenylazo)-phenylacetic acid (AMPP), into the backbone of a putative turn region within Aβ. AMPP adopts a rigid β-hairpin turn when azobenzene is in the cis conformation, and can adopt an extended “β-arc” turn in the trans-azobenzene conformation. The long lifetimes of these conformationally stable isomers permit detailed biochemical analyses that help to clarify the controversial role played by these two types of turns during the toxic misfolding pathway of Aβ. Methods to photo-nucleate the cis- or trans-AMPP isomeric turns in aqueous buffer are also described. Finally, we detail selected techniques to characterize the Aβ aggregates derived from these photoisomerized variants.

Original languageEnglish (US)
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Pages387-406
Number of pages20
DOIs
StatePublished - Jan 1 2018

Publication series

NameMethods in Molecular Biology
Volume1777
ISSN (Print)1064-3745

Keywords

  • Alzheimer’s disease
  • Amyloid-β
  • Azobenzene
  • Photoisomerization
  • Photoswitch
  • β-Arc
  • β-Hairpin

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