Organic Chemistry Seminar
Protein O-glycosylation is one of the most important co- and/or post-translational modifications. Based on previous studies, it is believed that O-glycosylation may significantly enhance the functional diversity of proteins by changing their conformation, stability, solubility, binding affinity, substrate specificity, and biological activity. However, due to the intrinsic complexity of glycoproteins, quantitative knowledge about the effects of protein O-glycosylation is largely lacking. We recently demonstrated that chemical synthesis can be employed as a useful tool to quantitatively analyze the effects of protein O-glycosylation and to define the molecular determinants of these effects. Our findings highlight the collective importance of the amino acid environment and glycan size, type, and linkage in controlling the effects of protein O-glycosylation. Going forward, our results suggest the possibility of designing proteins with multiple improved properties by simultaneously varying the structures of glycans and amino acids local to the glycosylation site.