Medicinal and Pharmaceutical Chemistry Commons^™

A Simple Method For Discovering Druggable, Specific Glycosaminoglycan-Protein Systems. Elucidation Of Key Principles From Heparin/Heparan Sulfate-Binding Proteins, Aurijit Sarkar, Umesh R. Desai

Psychology Publications

Glycosaminoglycans (GAGs) affect human physiology and pathology by modulating more than 500 proteins. GAG-protein interactions are generally assumed to be ionic and nonspecific, but specific interactions do exist. Here, we present a simple method to identify the GAG-binding site (GBS) on proteins that in turn helps predict high specific GAG–protein systems. Contrary to contemporary thinking, we found that the electrostatic potential at basic arginine and lysine residues neither identifies the GBS consistently, nor its specificity. GBSs are better identified by considering the potential at neutral hydrogen bond donors such as asparagine or glutamine sidechains. Our studies also reveal that an …