par Van Antwerpen, Pierre 
;Zouaoui Boudjeltia, Karim
Référence Free radical research, 49, 6, page (711-720)
Publication Publié, 2015-06
;Zouaoui Boudjeltia, Karim Référence Free radical research, 49, 6, page (711-720)
Publication Publié, 2015-06
Article révisé par les pairs
| Résumé : | Rational drug design is a general approach using protein-structure technique in which the discovery of a ligand can be driven either by chance, screening, or rational theory. Myeloperoxidase (MPO) was rapidly identified as a therapeutical target because of its involvement in chronic inflammatory syndromes. In this context, the research of MPO inhibitors was intensified and development of new chemical entities was rationally driven by the research of ligands that enter into the MPO catalytic pocket. Actually, as soon as crystallography data of MPO have become available and its structure was virtually designed, the rational drug design has been applied to this peroxidase. Pharmaceutical industries and academic laboratories apply rational drug design on MPO by either optimizing known inhibitors or searching new molecules by high-throughput virtual screening. By these ways, they were able to find efficient MPO inhibitors and understand their interactions with the enzyme. During this quest of MPO inhibition, it appears that Glu268 is a crucial residue in order to optimize ligandtarget interaction. This amino acid should be carefully considered by medicinal chemist when they design inhibitors interfering with MPO activity. |
