Chemoenzymatic synthesis of glycopeptides and glycoproteins through endoglycosidase-catalyzed transglycosylation.
Homogeneous glycopeptides and glycoproteins are indispensable for detailed structural and functional studies of glycoproteins. It is also fundamentally important to correct glycosylation patterns for developing effective glycoprotein-based therapeutics. This review discusses a useful chemoenzymatic method that takes advantage of the endoglycosidase-catalyzed transglycosylation to attach an intact oligosaccharide to a polypeptide in a single step, without the need for any protecting groups. The exploration of sugar oxazolines (enzymatic reaction intermediates) as donor substrates has not only expanded substrate availability, but also has significantly enhanced the enzymatic transglycosylation efficiency. Moreover, the discovery of a novel mutant with glycosynthase-like activity has made it possible to synthesize homogeneous glycoproteins with full-size natural N-glycans. Recent advances in this highly convergent chemoenzymatic approach and its application for glycopeptide and glycoprotein synthesis are highlighted.
Wang
Lai-Xi
LX
Institute of Human Virology and Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. LWang3@ihv.umaryland.edu
D000595:Amino Acid Sequence; D006020:Glycopeptides / Q000138:chemical synthesis*; D006023:Glycoproteins / Q000138:chemical synthesis*; D006026:Glycoside Hydrolases / Q000378:metabolism*; D006031:Glycosylation; D015700:HIV Envelope Protein gp41 / Q000138:chemical synthesis; D017038:Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase / Q000378:metabolism; D009844:Oligosaccharides / Q000737:chemistry; D010080:Oxazoles / Q000737:chemistry
D006020:Glycopeptides; D006023:Glycoproteins; D015700:HIV Envelope Protein gp41; D009844:Oligosaccharides; D010080:Oxazoles; D006026:Glycoside Hydrolases; D017038:Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase