Enhancing polo-like kinase 1 selectivity of polo-box domain-binding peptides

An important goal in the development of polo-like kinase 1 (Plk1) polo-box domain (PBD) binding inhibitors is selectivity for Plk1 relative to Plk2 and Plk3. In our current work we show that Plk1 PBD selectivity can be significantly enhanced by modulating interactions within a previously discovered cryptic pocket and a more recently identified proximal auxiliary pocket. Published by Elsevier Ltd.