Carbonic anhydrase activation and the drug design.
The activation mechanism of Carbonic Anhydrase was recently explained using kinetic, spectroscopic and X-ray techniques. It has been demonstrated that the activators molecules (CAAs) bind at the entrance of the enzyme active-site facilitating the rate-determining step of CA catalytic cycle. Drug design studies have been performed in order to obtain strong CAAs belonging to several chemical classes: amino acids, azoles, amine and their derivatives, etc. Structure-activity correlations of different activators are discussed for the most studied Carbonic Anhydrase isozymes: isoform I and II. The physiological relevance of CA activation and the possible application of CAAs in Alzheimer's disease and for other memory therapies are also treated.
Temperini
Claudia
C
Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy. claudia.temperini@unifi.it
Scozzafava
Andrea
A
Supuran
Claudiu T
CT
D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism; D002256:Carbonic Anhydrases / Q000737:chemistry* / Q000378:metabolism*; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D002256:Carbonic Anhydrases