Carbonic anhydrase inhibitors: The membrane-associated isoform XV is highly inhibited by inorganic anions

The membrane-associated mouse isozyme of carbonic anhydrase XV ( mCA XV), has been investigated for its interaction with anion inhibitors. mCA XV is an isoforms possessing a very particular inhibition pro. le by anions, dissimilar to that of all other mammalian CAs investigated earlier. Many simple inorganic anions ( thiocyanate, cyanide, azide, bicarbonate, hydrogen sulfide, bisulfite and sulfate) showed low micromolar inhibition constants against mCA XV ( K(I)s of 8.2-10.1 mu M), whereas they acted as much weaker ( usually millimolar) inhibitors of other isoforms. Halides, nitrate, nitrite, carbonate, sulfamate, sulfamide and phenylboronic/arsonic acid were weaker inhibitors, with inhibition constants in the range of 27.6-288 mu M. Our data may be useful for the design of more potent inhibitors of mCA XV ( considering various zinc binding groups present in the anions investigated here, e. g., the sulfonate one) and for understanding some physiologic/pharmacologic consequences of mCA XV inhibition by anions such as bicarbonate or sulfate which show quite high affinity for it. (C) 2008 Elsevier Ltd. All rights reserved.