A molecular chromatographic approach to analyze the cell diffusion of arginase inhibitors.
Our group demonstrated that arginase inhibition reduces endothelial dysfunction in spontaneously hypertensive rats [C. Demougeot, A. Prigent-Tessier, C. Marie, A. Berthelot, J. Hypertens. 23 (2005) 971; C. Demougeot, A. Prigent-Tessier, T. Bagnost, C. Andre, Y. Guillaume, M. Bouhaddi, C. Marie, A. Berthelot, Life Sci. 80 (2007) 1128] which opens perspectives in the development of drugs against hypertension. In previous papers [T. Bagnost, Y.C. Guillaume, M. Thomassin, J.F. Robert, A. Berthelot, A. Xicluna, C. Andre, J. Chromatogr. B: Analyt. Technol. Biomed. Life Sci. 856 (2007) 113; T. Bagnost, Y.C. Guillaume, M. Thomassin, A. Berthelot, C. Demougeot, C. Andre, J. Chromatogr. B: Analyt. Technol. Biomed. Life Sci. 873 (2008) 37], we developed a biochromatographic column for studying the binding of an arginase inhibitor with this enzyme and the effect of magnesium on this binding. In this paper, the interaction of arginase inhibitors with an immobilized artificial membrane (IAM) has been studied using a biochromatographic approach. This IAM provided a biophysical model system to study the inhibitor passive transport across cells. It was demonstrated that more the inhibitor cross the cell membrane by passive diffusion more it is potent. As well, an analysis of the thermodynamics of the interaction of the arginase inhibitors with the IAM showed that van der Waals, hydrogen and ionic bonds were the main forces between the arginase inhibitors and the polar head groups of the IAM surface.
Faculté de Médecine et de Pharmacie, Equipe Sciences Séparatives Biologiques et Pharmaceutiques, CHU Jean Minjoz, Université de Franche-Comté, Place Saint-Jacques, Besançon Cedex, France.
Teddy
T
Bagnost
Claire
C
André
Mireille
M
Thomassin
Alain
A
Berthelot
Céline
C
Demougeot
Yves Claude
YC
Guillaume
D001119:Arginase / Q000037:antagonists & inhibitors*; D002845:Chromatography / Q000379:methods*; D004058:Diffusion; D004791:Enzyme Inhibitors / Q000737:chemistry*; D007700:Kinetics; D008567:Membranes, Artificial
D004791:Enzyme Inhibitors; D008567:Membranes, Artificial; D001119:Arginase