Toward Fully Synthetic Carbohydrate-Based HIV Antigen Design:  On the Critical Role of Bivalency

Vadim Y. Dudkin,† Marianna Orlova,‡ Xudong Geng,† Mihirbaran Mandal,† William C. Olson,‡ and Samuel J. Danishefsky*†§
Laboratory for Bioorganic Chemistry, The Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, New York 10021, Progenics Pharmaceuticals, Inc. 777 Old Saw Mill River Rd., Tarrytown, New York 10591, and Department of Chemistry, Columbia University, Havemeyer Hall, New York, New York 10027
J. Am. Chem. Soc., 2004, 126 (31), pp 9560–9562
DOI: 10.1021/ja047720g
Publication Date (Web): July 14, 2004
Copyright © 2004 American Chemical Society
†

 The Sloan-Kettering Institute for Cancer Research.

,
‡

 Progenics Pharmaceuticals, Inc.

,
*

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

,
§

 Columbia University.

, s-danishefsky@ski.mskcc.org

Abstract

Abstract Image

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.

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History

  • Published In Issue August 11, 2004
  • Received April 20, 2004

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