Abstract
Di- and trivalent glycopeptide mimics of the HIV 2G12 epitope have been synthesized and evaluated for their comparative 2G12 binding characteristics. The epitope mimics consist of a cyclic peptide scaffold (unrelated to gp120 peptide sequences) attached via aspartate linkages to two or three copies of the high-mannose glycan, Man sub(9)GlcNAc sub(2). The synthesis has been achieved via high-yielding double and triple Lansbury aspartylations of Man sub(9)GlcNAc sub(2)-NH sub(2) with peptides containing, respectively, two and three aspartate residues. Conjugation of such constructs with an immunogenic carrier protein, OMPC, has been accomplished through the peptide's cysteine sulfhydryl function, and Biacore assays have shown that binding affinity for 2G12 increases with increasing valency.