Discovering the distinct inhibitory effects between C4-epimeric glycosyl amino acids: new insight into the development of protein tyrosine phosphatase inhibitors

Abstract

There has been increasing interest in the development of drug candidates based on sugar templates that possess rich structural and, especially, configurational diversities. We disclose herein that the epimeric identity between methyl 3,4-bis-phenylalanyl/tyrosinyl triazolyl-alpha-D-galactopyranoside and glucopyranoside may lead to their distinct inhibitory effects on specific protein tyrosine phosphatases (PTPs). Subsequently performed molecular docking study elucidated the plausible binding behaviors of the more potent galactosyl inhibitors with their primary PTP target, i.e. Cell Division Cycle 25B (CDC25B) phosphatase.