Venkitaraman A
Macrocyclization of an all-D linear α-helical peptide imparts cellular permeability
Peptide-based molecules hold great potential as targeted inhibitors of intracellular protein–protein interactions (PPIs). Indeed, the vast diversity of chemical space conferred through their primary, secondary and tertiary structures allows these molecules to be applied to targets that are typically deemed intractable via small molecules. However, the development of peptide therapeutics has been hindered by their limited conformational stability, proteolytic sensitivity and cell permeability.
ReadTargeting codon 158 p53-mutant cancers via the induction of p53 acetylation
Gain of function (GOF) DNA binding domain (DBD) mutations of TP53 upregulate chromatin regulatory genes that promote genome-wide histone methylation and acetylation. Here, we therapeutically exploit the oncogenic GOF mechanisms of p53 codon 158 (Arg158) mutation, a DBD mutant found to be prevalent in lung carcinomas.
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