Development of Polyvalent Inhibitors of HIV Cell Entry

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DESCRIPTION (provided by applicant): The goal of this proposed research is to investigate a strategy to block the entry of HIV into cells by amplifying the potency of known inhibitors using a polyvalent ligand presentation approach. I propose to create polymer scaffolds functionalized with known peptide inhibitors of HIV fusion, to exploit an enhanced avidity based on multivalent binding, and to compare the ability of these systems in preventing fusion with that of corresponding concentrations of the active ligand in monovalent form. A successful outcome of this work would be a demonstration that a ligand (or ligands) attached to a polymer is more successful in preventing cell fusion in a mammalian cell model of virus-cell fusion than is the same ligand (at the same equivalent concentration) in monomeric form. The first goal of this project is to develop extremely potent polyvalent inhibitors of HIV entry that may enable novel therapeutic regimens for the treatment of HIV infection. The second goal of this project is to develop cheap polyvalent inhibitors of HIV entry that are at least as potent as current, cost-prohibitive therapies, to enable their wider use.