Carbonic anhydrase II-induced selection of inhibitors from a dynamic combinatorial library of Schiff's bases.
A dynamic combinatorial library (DCL) has been generated under thermodynamic control by using the aminocarbonyl/imine interconversion as reversible chemistry, combined with non-covalent binding within the active site of the metalloenzyme human carbonic anhydrase II (hCA II, EC 4.2.1.1). The high affinity of hCA II isozyme towards some sulfonamide inhibitors obtained here was used to select from the dynamic library specific inhibitors of this isoform. These results point out to the possibility of identifying sulfonamide amplified compounds presenting potent inhibition and high yield of formation in the presence of the isoform(s) towards which the inhibitors were designed.
Nasr
Gihane
G
Institut Européen des Membranes, ENSCM-UMII-CNRS 5635, Place Eugène Bataillon, CC 047, F-34095 Montpellier, France.
Petit
Eddy
E
Supuran
Claudiu T
CT
Winum
Jean-Yves
JY
Barboiu
Mihail
M
D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D020134:Catalytic Domain; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D006801:Humans; D012545:Schiff Bases / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology; D013816:Thermodynamics
D002257:Carbonic Anhydrase Inhibitors; D012545:Schiff Bases; D013449:Sulfonamides; D024402:Carbonic Anhydrase II