Designer macrocyclic organo-peptide hybrids inhibit the interaction between p53 and HDM2/X by accommodating a functional α-helix

摘要

We report the design of side-chain-to-tail linked organo-peptide hybrids incorporating an α-helical protein-binding motif. Using this strategy, macrocyclic inhibitors of the p53:HDM2 interaction displaying dual specificity against the HDMX homolog as well as increased proteolytic stability could be obtained.