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 A. 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.
Laboratoire de Chimie Organique et Macromoléculaire, UMR CNRS 8009, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq, France.
Cédric
C
Maurin
Fabrice
F
Bailly
Eric
E
Buisine
Hervé
H
Vezin
Gladys
G
Mbemba
Jean François
JF
Mouscadet
Philippe
P
Cotelle
D002413:Cations, Divalent / Q000737:chemistry; D004578:Electron Spin Resonance Spectroscopy; D019427:HIV Integrase / Q000737:chemistry*; D008024:Ligands; D008274:Magnesium / Q000737:chemistry*; D008345:Manganese / Q000737:chemistry*; D013058:Mass Spectrometry; D008958:Models, Molecular; D015394:Molecular Structure; D019289:Pyruvic Acid / Q000031:analogs & derivatives* / Q000737:chemistry*
C493524:4-phenyl-4-oxo-2-hydroxybuten-2-oic acid; D002413:Cations, Divalent; D008024:Ligands; D008345:Manganese; D019289:Pyruvic Acid; D019427:HIV Integrase; D008274:Magnesium