title: Chemoenzymatic synthesis of HIV-1 gp41 glycopeptides: effects of glycosylation on the anti-HIV activity and alpha-helix bundle-forming ability of peptide C34.
abstract: C34 is a 34-mer peptide derived from the C-terminal ectodomain of HIV-1 envelope glycoprotein, gp41. The C34 region in native gp41 carries a conserved N-glycan at Asn637 and the sequence is directly involved in the virus-host membrane fusion, an essential step for HIV-1 infection. This paper describes the synthesis of glycoforms of C34 which carry a monosaccharide, a disaccharide, and a native oligosaccharide moiety. The synthesis of the glycopeptide which carries a native high-mannose type N-glycan was achieved by a chemoenzymatic approach by using an endoglycosidase-catalyzed oligosaccharide transfer as the key step. The effects of glycosylation on the inhibitory activity and the helix-bundle forming ability of C34 were investigated. It was found that glycosylation moderately decreases the anti-HIV activity of C34 and, in comparison with C34, glyco-C34 forms less compact six-helix bundles with the corresponding N-terminal peptide, N36. This study suggests that conserved glycosylation modulates the anti-HIV activity and conformations of the gp41 C-peptide, C34.
authors.affiliation: Institute of Human Virology, Biotechnology Institute, University of Maryland, 725 W. Lombard Street, Baltimore, MD 21201, USA. wangx@umbi.umd.edu
authors.forename: Lai-Xi
authors.initials: LX
authors.lastname: Wang
authors.forename: Haijing
authors.initials: H
authors.lastname: Song
authors.forename: Shuwen
authors.initials: S
authors.lastname: Liu
authors.forename: Hong
authors.initials: H
authors.lastname: Lu
authors.forename: Shibo
authors.initials: S
authors.lastname: Jiang
authors.forename: Jiahong
authors.initials: J
authors.lastname: Ni
authors.forename: Hengguang
authors.initials: H
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology; D001216:Asparagine / Q000737:chemistry; D006031:Glycosylation; D015700:HIV Envelope Protein gp41 / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011134:Polysaccharides / Q000737:chemistry; D017433:Protein Structure, Secondary
chemical_list: D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D011134:Polysaccharides; C407149:peptide C34; D001216:Asparagine