Chemical synthesis of highly congested gp120 V1V2 N-glycopeptide antigens for potential HIV-1-directed vaccines

J Am Chem Soc. 2013 Sep 4;135(35):13113-20. doi: 10.1021/ja405990z. Epub 2013 Aug 22.

Abstract

Critical to the search for an effective HIV-1 vaccine is the development of immunogens capable of inducing broadly neutralizing antibodies (BnAbs). A key first step in this process is to design immunogens that can be recognized by known BnAbs. The monoclonal antibody PG9 is a BnAb that neutralizes diverse strains of HIV-1 by targeting a conserved carbohydrate-protein epitope in the variable 1 and 2 (V1V2) region of the viral envelope. Important for recognition are two closely spaced N-glycans at Asn(160) and Asn(156). Glycopeptides containing this synthetically challenging bis-N-glycosylated motif were prepared by convergent assembly, and were shown to be antigenic for PG9. Synthetic glycopeptides such as these may be useful for the development of HIV-1 vaccines based on the envelope V1V2 BnAb epitope.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / chemistry
  • AIDS Vaccines / immunology*
  • Antigens / chemistry
  • Antigens / immunology*
  • Carbohydrate Conformation
  • Crystallography, X-Ray
  • Glycopeptides / chemistry
  • Glycopeptides / immunology*
  • HIV Envelope Protein gp120 / chemistry
  • HIV Envelope Protein gp120 / immunology*
  • HIV-1 / immunology*
  • Models, Molecular
  • Molecular Sequence Data

Substances

  • AIDS Vaccines
  • Antigens
  • Glycopeptides
  • HIV Envelope Protein gp120