Carbohydrate mimetic peptides are designable, they can carry T-cell epitopes and circumvent tolerance. A mimic-based HIV vaccine can be a viable alternative to carbohydratebased antigens if the diversity of epitopes found on gp120 can be recapitulated. To improve existing mimics, an attempt was made to study the structural correlates of the observed polyspecificity of carbohydrate mimetic peptides based on the Y[P/R]Y motif in more detail. A carbohydrate mimetic peptide - D002, (RGGLCYCRYRYCVCVGR), bound a number of lectins with different specificities. While this peptide reacted strongly with both Lotus and Concanavalin A (ConA) lectins, it bound to Lotus stronger than Con A. By varying the central motif RYRY, five versions were produced in MAP format and their avidity for Lotus and ConA lectins was tested by SPR. Although the kinetic parameters were similar, the version based on the sequence YPYRY had an optimal affinity for both lectins as well as improved avidity for WGA and PHA. Thus, as far as lectin specificity is concerned, YPYRY had improved multiple antigenic properties. Both RYRY and YPYRY precipitated antibodies from human IgG for intravenous use that bound to gp120 in vitro and immunoprecipitated gp120 from transfected CHO-PI cells. Thus, Y[P/R]Y motifs mimic multiple carbohydrate epitopes, many of which are found on HIV and a preimmune human IgG antibodies that bind to HIV carbohydrates cross-react to a comparable extent with both RYRY and YPYRY carbohydrate mimetic peptides.