Chemical Synthesis of Homogeneous Human E-Cadherin N-Linked Glycopeptides: Stereoselective Convergent Glycosylation and Chemoselective Solid-Phase Aspartylation.

Abstract

We report herein an efficient chemical synthesis of homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide. The key steps are a chemoselective on-resin aspartylation using a pseudoproline-containing peptide and stereoselective glycosylation using glycosyl fluororide as a donor. This synthetic strategy demonstrates potential utility in accessing a wide range of homogeneous N-linked glycopeptides for the examination of their biological function.