Spectroscopic Studies of Diketoacids−Metal Interactions. A Probing Tool for the Pharmacophoric Intermetallic Distance in the HIV-1 Integrase Active Site

The interactions with divalent cations of 4-phenyl-4-oxo-2-hydroxybuten-2-oic acid (benzoylpyruvic 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 4−6 Å. 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.