Improve Stability of Bioactive Peptides by Enzymatic Modular Synthesis of Peptides with O-Linked Sialyl Lewis x

Glycosylation is an effective solution for peptide drug modification to overcome limitations such as instability under physiological conditions and lack of receptor selectivity. Disclosed herein is a facile enzymatic modular assembly strategy for the (semi)preparative-scale synthesis of active glycopeptides. Sialyl Lewis x (sLex) oligosaccharides with E-selectin-targeting activity can be conjugated with peptides through multistep enzymatic reactions. The antiangiogenic peptide ES2 and anticancer peptide citropin 1.1 were successfully modified without loss of their biological activities. The half-lives of the glycopeptides were approximately 64-fold (ES2-sLex) and 28-fold (citropin-sLex) higher than that of the unmodified peptides in human serum.