Rational Structure-Based Design of Fluorescent Probes for Amyloid Folds

Chembiochem. 2019 May 2;20(9):1161-1166. doi: 10.1002/cbic.201800664. Epub 2019 Mar 7.

Abstract

Amyloid fibrils are pathological hallmarks of various human diseases, including Parkinson's, Alzheimer's, amyotrophic lateral sclerosis (ALS or motor neurone disease), and prion diseases. Treatment of the amyloid diseases are hindered, among other factors, by timely detection and therefore, early detection of the amyloid fibrils would be beneficial for treatment against these disorders. Here, a small molecular fluorescent probe is reported that selectively recognize the fibrillar form of amyloid beta(1-42), α-synuclein, and HET-s(218-289) protein over their monomeric conformation. The rational design of the reporters relies on the well-known cross-β-sheet repetition motif, the key structural feature of amyloids.

Keywords: Abeta(1-42); HET-s; alpha-synuclein; amyloid fibrils; fluorescence probes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / metabolism*
  • Fluorescence
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / metabolism*
  • Fungal Proteins / metabolism*
  • Humans
  • Molecular Structure
  • Peptide Fragments / metabolism*
  • Podospora / chemistry
  • Protein Binding
  • Spectrometry, Fluorescence
  • alpha-Synuclein / metabolism*

Substances

  • Amyloid beta-Peptides
  • Fluorescent Dyes
  • Fungal Proteins
  • Peptide Fragments
  • alpha-Synuclein
  • amyloid beta-protein (1-42)