CARB 77 |
| N-linked glycosylation is one of the most common posttranslational modifications of proteins in eukaryotes. The oligosaccharide components are implicated to play important roles in modulating glycoprotein's structure and functions, such as folding, stability, cell adhesion, immune recognition, and serum half-life. HIV-1 has two envelope glycoproteins, gp120 and gp41. HIV-1 gp120 typically bears 24 N-glycans (11 high-mannose type and 13 complex type) and the gp41 possesses 4 conserved N-glycans. Although the carbohydrates have been implicated to play important roles in HIV immune evasion and to serve as ligands for sexual transmission of HIV, the precise functions of individual HIV-1 N-glycans, e.g., their effects on protein domain's conformations and immunogenicity, are largely unknown, mainly because of the structural micro-heterogeneity of the envelope glycoproteins. We believe that these problems can be adequately addressed through synthesis and functional studies of homogeneous HIV-1 glycopeptides. This paper will discuss a highly efficient endoglycosidase-catalyzed synthesis of N-glycopeptides using sugar oxazolines as the donor substrates. The enzymatic transfer of an oligosaccharide moiety from the sugar oxazoline to the GlcNAc-peptide acceptor in a single step allows a highly convergent synthetic approach. This chemoenzymatic approach has enabled us to synthesize some important HIV-1 glycopeptides such as the glycoforms of gp41 C34 and the V3 domain glycopeptides of gp120. The total synthesis of larger HIV-1 glycopeptides carrying full-size high-mannose or complex type N-glycans are in progress. The results will be discussed in the presentation. |
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General Papers: Synthesis of Carbohydrates and Derivatives
1:30 PM-5:10 PM, Wednesday, 29 March 2006 Georgia World Congress Center -- B409, Oral
Division of Carbohydrate Chemistry |