Carbonic anhydrase inhibitors:: The β-carbonic anhydrase from Helicobacter pylori is a new target for sulfonamide and sulfamate inhibitors

DNA clones for the P-class carbonic anhydrase (CA, EC 4.2.1.1) of Helicobactor pylori (hp beta CA) were obtained. A recombinant hp beta CA protein lacking the N-terminal 15-arnino acid residues was produced and purified, representing a catalytically efficient CA. hp beta CA was strongly inhibited (K(1)s in the range of 24-45 nM) by many sulfonamides/sulfamates, among which acetazolamide, ethoxzolamide, topiramate, and sulpiride, all clinically used drugs. The dual inhibition of alpha- and/or beta-class CAs of H. pylori might represent a useful alternative for the management of gastritis/gastric ulcers, as well as gastric cancer. This is also the first study showing that a bacterial beta-CA can be a drug target. (c) 2007 Elsevier Ltd. All rights reserved.