Irreversible inhibition of aldolase by a phosphorylated a-dicarbonyl compound

Nicolas Chabot (1) , Virginie Vinatier (1) , Thierry Gefflaut (2) , Cécile Baudoin-Dehoux (1) , Frédéric Rodriguez (1) , Casimir Blonski (1) , Pascal Hoffmann (1)

1 SPCMIB - Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique
2 SEESIB - Synthèse et étude de systèmes à intêret biologique

The preparation of a phosphorylated alpha-dicarbonyl compound designed to specifically react with arginine residues of enzymes accepting phosphorylated compounds as effectors is reported, and shown to inhibit rabbit muscle aldolase in a time-dependent and irreversible manner. This irreversible inhibition occured in a buffer devoid of borate ions, suggesting that the presence of the phosphate moiety contributes in the stabilization of the adduct formed with arginine residues. Under the same conditions, the metalloenzyme iron superoxide dismutase, in which an arginine is known to be critical for the catalytic function, is not significantly inhibited.

Domaines: Chimie

Nicolas Chabot, Virginie Vinatier, Thierry Gefflaut, Cécile Baudoin-Dehoux, Frédéric Rodriguez, et al.. Irreversible inhibition of aldolase by a phosphorylated a-dicarbonyl compound. Journal of Enzyme Inhibition and Medicinal Chemistry, 2008, 23, pp.21-27. ⟨10.1080/14756360701383718⟩. ⟨hal-00258862⟩