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.
Maurin
Cédric
C
Laboratoire de Chimie Organique et Macromoléculaire, UMR CNRS 8009, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq, France.
Bailly
Fabrice
F
Buisine
Eric
E
Vezin
Hervé
H
Mbemba
Gladys
G
Mouscadet
Jean François
JF
Cotelle
Philippe
P
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