Application of oxime-diversification to optimize ligand interactions within a cryptic pocket of the polo-like kinase 1 polo-box domain

Cover of Bioorganic & Medicinal Chemistry Letters Oct. 15, 2016

By a process involving initial screening of a set of 87 aldehydes using an oxime ligation-based strategy, we were able to achieve a several-fold affinity enhancement over one of the most potent previously known polo-like kinase 1 (Plk1) polo-box domain (PBD) binding inhibitors. This improved binding may result by accessing a newly identified auxiliary region proximal to a key hydrophobic cryptic pocket on the surface of the protein. Our findings could have general applicability to the design of PBD-binding antagonists. 
Cover design by Joseph Myer

Chemical Biology Laboratory

Xue Zhi Zhao, David Hymel and Terrence R. Burke, Jr. in Bioorganic & Medicinal Chemistry Letters2016, 26, 5009-5012. 

Published Date: 
October, 2016