Chemoenzymatic synthesis of HIV-1 gp41 glycopeptides: Effects of glycosylation on the anti-HIV activity and α-helix bundle-forming ability of peptide C34

Abstract

C34 is a34-mer peptide derived 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-glycans 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. © 2005 Wiley-VCH Verlag GmbH & Co. KGaA.