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An α-Helix-Mimicking 12,13-Helix: Designed α/β/γ-Foldamers as Selective Inhibitors of Protein-Protein Interactions.

Claire M GrisonJennifer A MilesSylvie RobinAndrew J WilsonDavid J Aitken
Published in: Angewandte Chemie (International ed. in English) (2016)
A major current challenge in bioorganic chemistry is the identification of effective mimics of protein secondary structures that act as inhibitors of protein-protein interactions (PPIs). In this work, trans-2-aminocyclobutanecarboxylic acid (tACBC) was used as the key β-amino acid component in the design of α/β/γ-peptides to structurally mimic a native α-helix. Suitably functionalized α/β/γ-peptides assume an α-helix-mimicking 12,13-helix conformation in solution, exhibit enhanced proteolytic stability in comparison to the wild-type α-peptide parent sequence from which they are derived, and act as selective inhibitors of the p53/hDM2 interaction.
Keyphrases
  • amino acid
  • dna binding
  • wild type
  • high resolution
  • quantum dots
  • molecular dynamics simulations
  • mass spectrometry
  • binding protein
  • protein protein
  • simultaneous determination