Toward fully synthetic carbohydrate-based HIV antigen design: on the critical role of bivalency.
Synthetic gp120331-335 glycopeptide fragments carrying hybrid and high-mannose type N-linked glycans were evaluated for binding to broadly neutralizing antibody 2G12 using surface plasmon resonance technology. None of the hybrid-type constructs demonstrated binding to 2G12. In the high-mannose series, the "Cys dimer" construct, presenting two undecasaccharide glycans, showed significantly higher binding than the Cys-protected monomer. The binding of the dimeric structure was further investigated in competition with recombinant gp120. The data suggest that gp120 and its designed synthetic epitope construct bind to the same site on 2G12.
Laboratory for Bioorganic Chemistry, The Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, New York 10021, USA.
Vadim Y
VY
Dudkin
Marianna
M
Orlova
Xudong
X
Geng
Mihirbaran
M
Mandal
William C
WC
Olson
Samuel J
SJ
Danishefsky
D002240:Carbohydrate Sequence; D002241:Carbohydrates / Q000138:chemical synthesis* / Q000276:immunology; D006020:Glycopeptides / Q000138:chemical synthesis* / Q000276:immunology; D015488:HIV Antigens / Q000737:chemistry*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000276:immunology; D008358:Mannose / Q000031:analogs & derivatives / Q000138:chemical synthesis; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology
D002241:Carbohydrates; D006020:Glycopeptides; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D010446:Peptide Fragments; D008358:Mannose