TY - JOUR
T1 - Cloning, expression, post-translational modifications and inhibition studies on the latest mammalian carbonic anhydrase isoform, CA XV
AU - Hilvo, Mika
AU - Salzano, Anna Maria
AU - Innocenti, Alessio
AU - Kulomaa, Markku S.
AU - Scozzafava, Andrea
AU - Scaloni, Andrea
AU - Parkkila, Seppo
AU - Supuran, Claudiu T.
PY - 2009
Y1 - 2009
N2 - We have cloned and purified to homogeneity the latest member of the mammalian α-carbonic anhydrase (CA, EC 4.2.1.1) family, the mouse CA XV (mCA XV) protein. An investigation on the post-translational modifications of the enzyme has also been performed. The enzyme shows a moderate catalytic activity for the physiologic reaction, similarly to the physiologically relevant isoforms CA I, IV, VI, XII, and XIV, and it is susceptible to inhibition by sulfonamides and sulfamates. Best mCA XV inhibitors were celecoxib, sulfanilyl-sulfonamides, methazolamide, ethoxzolamide, dorzolamide, brinzolamide, and sulthiame, with KIs in the range of 45−65 nM. Due to the presence of this enzyme in rather high amounts in the rodent kidneys, the contribution of this isoform to the overall drug response should be taken into account when animal models are used to investigate CA inhibitors.
AB - We have cloned and purified to homogeneity the latest member of the mammalian α-carbonic anhydrase (CA, EC 4.2.1.1) family, the mouse CA XV (mCA XV) protein. An investigation on the post-translational modifications of the enzyme has also been performed. The enzyme shows a moderate catalytic activity for the physiologic reaction, similarly to the physiologically relevant isoforms CA I, IV, VI, XII, and XIV, and it is susceptible to inhibition by sulfonamides and sulfamates. Best mCA XV inhibitors were celecoxib, sulfanilyl-sulfonamides, methazolamide, ethoxzolamide, dorzolamide, brinzolamide, and sulthiame, with KIs in the range of 45−65 nM. Due to the presence of this enzyme in rather high amounts in the rodent kidneys, the contribution of this isoform to the overall drug response should be taken into account when animal models are used to investigate CA inhibitors.
UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-61449129341&partnerID=MN8TOARS
U2 - 10.1021/jm801267c
DO - 10.1021/jm801267c
M3 - Article
SN - 0022-2623
VL - 52
SP - 646
EP - 654
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 3
ER -