Selective and potent proteomimetic inhibitors of intracellular protein-protein interactions

Angew Chem Int Ed Engl. 2015 Mar 2;54(10):2960-5. doi: 10.1002/anie.201410810. Epub 2015 Feb 4.

Abstract

Inhibition of protein-protein interactions (PPIs) represents a major challenge in chemical biology and drug discovery. α-Helix mediated PPIs may be amenable to modulation using generic chemotypes, termed "proteomimetics", which can be assembled in a modular manner to reproduce the vectoral presentation of key side chains found on a helical motif from one partner within the PPI. In this work, it is demonstrated that by using a library of N-alkylated aromatic oligoamide helix mimetics, potent helix mimetics which reproduce their biophysical binding selectivity in a cellular context can be identified.

Keywords: apoptosis; foldamers; helical structures; peptidomimetics; protein-protein interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Humans
  • Molecular Mimicry*
  • Proteins / chemistry*

Substances

  • Proteins