A Modular Synthesis of Conformationally Preorganised Extended β-Strand Peptidomimetics

Tohru Yamashita, Peter C. Knipe, Nathalie Busschaert, Sam Thompson, Andrew D. Hamilton

Research output: Contribution to journalArticle

Abstract

A promising strategy for mediating protein-protein interactions is the use of non-peptidic mimics of secondary structural protein elements, such as the α-helix. Recent work has expanded the scope of this approach by providing proof-of-principle scaffolds that are conformationally biased to mimic the projection of side-chains from one face of another common secondary structural element - the β-strand. Herein, we present a synthetic route that has key advantages over previous work: monomers bearing an amino acid side-chain were pre-formed before rapid assembly to peptidomimetics through a modular, iterative strategy. The resultant oligomers of alternating pyridyl and six-membered cyclic ureas accurately reproduce a recognition domain of several amino acid residues of a β-strand, demonstrated herein by mimicry of the i, i+2, i+4 and i+6 residues.

Original languageEnglish (US)
Pages (from-to)14699-14702
Number of pages4
JournalChemistry - A European Journal
Volume21
Issue number42
DOIs
StatePublished - Oct 1 2015

Keywords

  • dipolar repulsion
  • extended conformations
  • foldamers
  • inhibitors
  • protein-protein interactions

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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