METHODS AND COMPOSITIONS FOR THE TREATMENT OR PREVENTION OF HUMAN IMMUNODEFICIENCY VIRUS INFECTION

摘要

A conserved cluster of oligomannose glycans on gp120 has been identified as the epitope recognized by the broadly HIV-1-neutralizing monoclonal antibody 2G12. Oligomannose glycans are also the ligands for DC-SIGN, a C-type lectin found on the surface of dendritic cells. Multivalency is fundamental for carbohydrate-protein interactions, and mimicking of the high glycan density on the virus surface has become essential for designing carbohydrate-based HIV vaccines and antiviral agents. Synthesis of oligomannose dendrons, which display multivalent oligomannoses in high density, and characterize their interaction with 2G12 and DC-SIGN by a glycan microarray binding assay is disclosed. These glycodendrons inhibit the binding of gp120 to 2G12 and recombinant dimeric DC-SIGN with IC50 in the nanomolar range. A second-generation Man9 dendron was identified as a potential immunogen for HIV vaccine development and as a potential antiviral agent.