Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 11096-11100 |
| Number of pages | 5 |
| Journal | Angewandte Chemie - International Edition |
| Volume | 55 |
| Issue number | 37 |
| DOIs | |
| Publication status | Published - 5 Sept 2016 |
Bibliographical note
Funding Information:The award of a French MESR doctoral research scholarship (to C.M.G.) is acknowledged. The European Research Council [ERC-PoC 632207], Leverhulme Trust [RPG-2013-065] and The Wellcome Trust [104920/Z/14/Z] are acknowledged for financial support of this research. The authors thank Arnout Kalverda and Gary Thompson for assistance with HSQC experiments and Jean-Pierre Baltaze for help with ROESY experiments.
Publisher Copyright:
© 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
Keywords
- foldamers
- inhibitors
- peptidomimetics
- protein–protein interactions
- α-helix mimetics
ASJC Scopus subject areas
- Catalysis
- General Chemistry