<i>De novo</i> coiled-coil peptides as scaffolds for disrupting protein-protein interactions.

ABSTRACT: Protein-protein interactions (PPIs) play pivotal roles in the majority of biological processes. Therefore, improved approaches to target and disrupt PPIs would provide tools for chemical biology and leads for therapeutic development. PPIs with α-helical components are appealing targets given that the secondary structure is well understood and can be mimicked or stabilised to render small-molecule and constrained-peptide-based inhibitors. Here we present a strategy to target α-helix-mediated PPIs that exploits de novo coiled-coil assemblies and test this using the MCL-1/NOXA-B PPI. First, computational alanine scanning is used to identify key α-helical residues from NOXA-B that contribute to the interface. Next, these residues are grafted onto the exposed surfaces of de novo d

SUBMITTER: Fletcher JM 

PROVIDER: S-EPMC6182421 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature