TY - JOUR
T1 - Anion inhibition studies of a β-carbonic anhydrase from Clostridium perfringens
AU - Vullo, Daniela
AU - Sai Kumar, R. Siva
AU - Scozzafava, Andrea
AU - Capasso, Clemente
AU - Ferry, James G.
AU - Supuran, Claudiu T.
N1 - Funding Information:
This work was financed in part by two FP7 EU project (Metoxia and Dynano, to C.T.S. and A.S.), and by the Pennsylvania State University Person Endowment (to J.G.F.).
PY - 2013/12/15
Y1 - 2013/12/15
N2 - A β-carbonic anhydrases (CAs, EC 4.2.1.1) was recently cloned, purified and characterized kinetically in the pathogen Clostridium perfringens. We report here the first inhibition study of this enzyme (CpeCA). CpeCA was poorly inhibited by iodide and bromide, and was inhibited with KIs in the range of 1-10 mM by a range of anions such as (thio)cyanate, azide, bicarbonate, nitrate, nitrite, hydrogensulfite, hydrogensulfide, stannate, tellurate, pyrophosphate, divanadate, tetraborate, peroxydisulfate, sulfate, iminodisulfonate and fluorosulfonate. Better inhibitory power, with K Is of 0.36-1.0 mM, was observed for cyanide, carbonate, selenate, selenocyanide, trithiocarbonate and diethyldithiocarbamate, whereas the best CpeCA inhibitors were sulfamate, sulfamide, phenylboronic acid and phenylarsonic acid, which had KIs in the range of 7-75 μM. This study thus provides the basis for developing better clostridial enzyme inhibitors with potential as antiinfectives with a new mechanism of action.
AB - A β-carbonic anhydrases (CAs, EC 4.2.1.1) was recently cloned, purified and characterized kinetically in the pathogen Clostridium perfringens. We report here the first inhibition study of this enzyme (CpeCA). CpeCA was poorly inhibited by iodide and bromide, and was inhibited with KIs in the range of 1-10 mM by a range of anions such as (thio)cyanate, azide, bicarbonate, nitrate, nitrite, hydrogensulfite, hydrogensulfide, stannate, tellurate, pyrophosphate, divanadate, tetraborate, peroxydisulfate, sulfate, iminodisulfonate and fluorosulfonate. Better inhibitory power, with K Is of 0.36-1.0 mM, was observed for cyanide, carbonate, selenate, selenocyanide, trithiocarbonate and diethyldithiocarbamate, whereas the best CpeCA inhibitors were sulfamate, sulfamide, phenylboronic acid and phenylarsonic acid, which had KIs in the range of 7-75 μM. This study thus provides the basis for developing better clostridial enzyme inhibitors with potential as antiinfectives with a new mechanism of action.
UR - http://www.scopus.com/inward/record.url?scp=84888875137&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84888875137&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2013.10.037
DO - 10.1016/j.bmcl.2013.10.037
M3 - Article
C2 - 24210500
AN - SCOPUS:84888875137
VL - 23
SP - 6706
EP - 6710
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 24
ER -