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An α‐Helix‐Mimicking 12,13‐Helix: Designed α/β/γ‐Foldamers as Selective Inhibitors of Protein–Protein Interactions
Author(s) -
Grison Claire M.,
Miles Jennifer A.,
Robin Sylvie,
Wilson Andrew J.,
Aitken David J.
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201604517
Subject(s) - chemistry , helix (gastropod) , peptidomimetic , peptide , bioorganic chemistry , protein design , stereochemistry , combinatorial chemistry , protein–protein interaction , protein secondary structure , peptide sequence , protein structure , biochemistry , enzyme , biology , ecology , snail , gene
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 ( t ACBC) 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/ h DM2 interaction.