ANTI-HIV PHARMACEUTICAL TARGETING CD4

The first stage of HIV infection begins with the viral particle binding to the CD4 protein on target cells. HIV binds to the first extracellular domain of CD4 (Domain 1). The goal of this research is to identify a high-affinity ligand for this region of CD4 and block the binding of HIV. We will make use of an "oriented peptide library" approach that selects high-affinity binders from a highly diverse peptide mixture library, typically containing billions of peptides. Domains and 2 (amino acids 1- 183) of CD4 (CD4(183)) will be expressed, purified and immobilized. Highly diverse peptide libraries will be synthesized and allowed to interact with CD4(183). From the sub-population of peptides binding to CD4(183), the consensus binding motif of the high affinity binders will be deduced through Edman sequencing. These peptide ligands will be synthesized and analyzed for gp120 binding inhibition. Finally, the peptide lead series will be further modified to increase their potency and enhance pharmaceutical properties.