Spectroscopic studies of diketoacids-metal interactions. A probing tool for the pharmacophoric intermetallic distance in the HIV-1 integrase active site

摘要

The interactions with divalent cations of 4-phenyl-4-oxo-2-hydroxybuten-2-oic acid (benzoyl-pyruvic acid (BPA)), the pharmacophore of HIV-1 integrase inhibitors, were investigated using spectroscopic tools. In the absence of the enzyme, a 2:2 metal-ligand complex was characterized with an intermetallic distance of 4-6Angstrom. Molecular modeling allowed us to propose a compatible structure for the metal-ligand complex. BPA does not inhibit the reactions catalyzed by HIV-1 IN, emphasizing the importance of the aromatic ring substitution in the antiviral activity.