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

58 Citations (Scopus)

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.

LanguageEnglish
Pages14699-14702
Number of pages4
JournalChemistry - A European Journal
Volume21
Issue number42
Early online date17 Aug 2015
DOIs
Publication statusPublished - 12 Oct 2015
Externally publishedYes

Fingerprint

Peptidomimetics
Proteins
Amino Acids
Amino acids
Bearings (structural)
Urea
Oligomers
Scaffolds
Monomers
beta-Strand Protein Conformation
alpha-Helical Protein Conformation
Protein Structural Elements

Keywords

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

Cite this

Yamashita, Tohru ; Knipe, Peter C. ; Busschaert, Nathalie ; Thompson, Sam ; Hamilton, Andrew D. / A Modular Synthesis of Conformationally Preorganised Extended β-Strand Peptidomimetics. In: Chemistry - A European Journal. 2015 ; Vol. 21, No. 42. pp. 14699-14702.
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A Modular Synthesis of Conformationally Preorganised Extended β-Strand Peptidomimetics. / Yamashita, Tohru; Knipe, Peter C.; Busschaert, Nathalie; Thompson, Sam; Hamilton, Andrew D.

In: Chemistry - A European Journal, Vol. 21, No. 42, 12.10.2015, p. 14699-14702.

Research output: Contribution to journalArticle

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