Elucidating the Function of Complex‐Type Oligosaccharides by Use of Chemical Synthesis of Homogeneous Glycoproteins

Abstract

AbstractProtein glycosylation is a major post‐translational modification. To elucidate the effect of this modification on protein function, homogeneous glycoproteins are required. Because glycoproteins isolated from biological sources contain glycoforms, a mixture of a single protein chain with several different oligosaccharides appended, homogeneous glycoproteins obtained through chemical synthesis offer a better solution. In this review, several methods used by our group for the chemical synthesis of homogeneous glycoproteins are addressed. First, preparation of sufficient amounts of oligosaccharides with the desired structures was achieved using a combination of chemical protection and enzymatic digestion. Then glycopeptide‐αthioesters were prepared by incorporation of oligosaccharides onto the side chains of cysteine residues in peptide‐αthioesters. Finally, biologically active homogeneous glycoproteins were prepared through native chemical ligation of glycopeptide‐αthioesters and subsequent oxidative folding.