Carbonic Anhydrase Activation and the Drug Design

Claudia      Temperini; Andrea      Scozzafava; Claudiu   T.   Supuran

Abstract

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 ratedetermining step of CA catalitic 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 Alzheimers desease and for other memory therapies are also treated.

Keywords: Carbonic anhydrase, X-ray structure, kinetic, enzyme activator, Alzheimer's desease