title: Introducing N-glycans into natural products through a chemoenzymatic approach.
abstract: The present study describes an efficient chemoenzymatic method for introducing a core N-glycan of glycoprotein origin into various lipophilic natural products. It was found that the endo-beta-N-acetylglucosaminidase from Arthrobactor protophormiae (Endo-A) had broad substrate specificity and can accommodate a wide range of glucose (Glc)- or N-acetylglucosamine (GlcNAc)-containing natural products as acceptors for transglycosylation, when an N-glycan oxazoline was used as a donor substrate. Using lithocholic acid as a model compound, we have shown that introduction of an N-glycan could be achieved by a two-step approach: chemical glycosylation to introduce a monosaccharide (Glc or GlcNAc) as a handle, and then Endo-A catalyzed transglycosylation to accomplish the site-specific N-glycan attachment. For those natural products that already carry terminal Glc or GlcNAc residues, direct enzymatic transglycosylation using sugar oxazoline as the donor substrate was achievable to introduce an N-glycan. It was also demonstrated that simultaneous double glycosylation could be fulfilled when the natural product contains two Glc residues. This chemoenzymatic method is concise, site-specific, and highly convergent. Because N-glycans of glycoprotein origin can serve as ligands for diverse lectins and cell-surface receptors, introduction of a defined N-glycan into biologically significant natural products may bestow novel properties onto these natural products for drug discovery and development.
authors.affiliation: Institute of Human Virology and Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Ochiai
authors.forename: Xinyu
authors.initials: X
authors.lastname: Zhang
authors.forename: Lai-Xi
authors.initials: LX
authors.lastname: Wang
mesh_terms: D000117:Acetylglucosamine / Q000737:chemistry / Q000378:metabolism; D001688:Biological Products / Q000096:biosynthesis / Q000737:chemistry; D002236:Carbohydrate Conformation; D006023:Glycoproteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000378:metabolism; D006027:Glycosides / Q000737:chemistry; D006031:Glycosylation; D007202:Indicators and Reagents; D008958:Models, Molecular; D009005:Monosaccharides / Q000378:metabolism; D010081:Oxazolone / Q000031:analogs & derivatives / Q000737:chemistry; D011134:Polysaccharides / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D001688:Biological Products; D006023:Glycoproteins; D006027:Glycosides; D007202:Indicators and Reagents; D009005:Monosaccharides; D011134:Polysaccharides; C461065:trifluoromethyloxazolinone; D010081:Oxazolone; D006026:Glycoside Hydrolases; D000117:Acetylglucosamine