Reversal of aggregation using β-breaker dipeptide containing peptides: Application to Aβ(1-40) self-assembly and its inhibition

ACS Chem Neurosci. 2014 May 21;5(5):400-8. doi: 10.1021/cn500064z. Epub 2014 Apr 3.

Abstract

Reversion of protein or peptide aggregation is a formidable task, important in various domains of research at the interface of chemistry, medicine, and nanoscience. A novel class of dipeptides, termed as β-breaker dipeptides (BBDPs), is identified, which can be incorporated into the self-recognizing sequences to generate a novel class of conformational switch which forms β-sheet at an initial stage and then converts in a controlled manner to random coil at specific conditions. Incorporation of BBDPs in a well designed amyloidogenic peptides generates a special class of β-sheet breaker peptides those undergo a chemical change at physiological condition generating a breaker element in situ. These β-breaker peptides are shown to first incorporate into the amyloid and then disrupt it. Such conformational switches may be used to study agrregation/disaggregation process and may find many biomedical applications relevant to aggregation related disorders. Such strategy for reversion of peptide aggregation using chemical tricks may find application in material chemistry as well.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / chemistry*
  • Amyloid beta-Peptides / pharmacology*
  • Amyloid beta-Peptides / ultrastructure
  • Dipeptides / chemistry
  • Humans
  • Peptide Fragments / chemistry*
  • Peptide Fragments / ultrastructure
  • Protein Aggregates / drug effects*
  • Protein Binding / drug effects
  • Protein Structure, Secondary
  • Time Factors

Substances

  • Amyloid beta-Peptides
  • Dipeptides
  • Peptide Fragments
  • Protein Aggregates