Efficient development of stable and highly functionalised peptides targeting the CK2α/CK2β protein-protein interaction.

ABSTRACT: The discovery of new Protein-Protein Interaction (PPI) modulators is currently limited by the difficulties associated with the design and synthesis of selective small molecule inhibitors. Peptides are a potential solution for disrupting PPIs; however, they typically suffer from poor stability in vivo and limited tissue penetration hampering their wide spread use as new chemical biology tools and potential therapeutics. In this work, a combination of CuAAC chemistry, molecular modelling, X-ray crystallography, and biological validation allowed us to develop highly functionalised peptide PPI inhibitors of the protein CK2. The lead peptide, CAM7117, prevents the formation of the holoenzyme assembly in vitro, slows down proliferation, induces apoptosis in cancer cells and

SUBMITTER: Iegre J 

PROVIDER: S-EPMC6530537 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature