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A dynamic target-based pharmacophoric model mapping the CD4 binding site on HIV-1 gp120 to identify new inhibitors of gp120–CD4 protein–protein interactions

2009; Elsevier BV; Volume: 19; Issue: 21 Linguagem: Inglês

10.1016/j.bmcl.2009.09.029

1464-3405

Fabiana Caporuscio, Andrea Tafi, Emmanuel González, Fabrizio Manetti, José A. Esté, Maurizio Botta,

Protein Structure and Dynamics

A dynamic target-based pharmacophoric model mapping the CD4 binding site on HIV-1 gp120 was built and used to identify new hits able to inhibit gp120-CD4 protein-protein interactions. Two compounds showed micromolar inhibition of HIV-1 replication in cells attributable to an interference with the entry step of infection, by direct interaction with gp120. Inactivity of compounds toward a M475I strain suggested specific contacts with the Phe43 cavity of gp120.