α-Helix mimetics as inhibitors of protein-protein interactions

Ishu Saraogi, Andrew D. Hamilton

Research output: Contribution to journalArticlepeer-review

Abstract

The inhibition of protein-protein interactions using small molecules is a viable approach for the treatment of a range of pathological conditions that result from a malfunctioning of these interactions. Our strategy for the design of such agents involves the mimicry of side-chain residues on one face of the α-helix; these residues frequently play a key role in mediating protein-protein interactions. The first-generation terphenyl scaffold, with a 3,2′,2″-substitution pattern, is able to successfully mimic key helix residues and disrupt therapeutically relevant interactions, including the Bcl-XLL-Bak and the p53-hDM2 (human double minute 2) interactions that are implicated in cancer. The second- and third-generation scaffolds have resulted in greater synthetic accessibility and more drug-like character in these molecules.

Original languageEnglish (US)
Pages (from-to)1414-1417
Number of pages4
JournalBiochemical Society Transactions
Volume36
Issue number6
DOIs
StatePublished - 2008

Keywords

  • Helix mimetic
  • Inhibitor
  • Medicinal chemistry
  • Protein-protein interaction
  • Rational design

ASJC Scopus subject areas

  • Biochemistry

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