Abstract:
:Metal complexing anions represent an important class of inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). The first inhibition study of the transmembrane isozymes CA XII (tumor-associated) and XIV with anions is reported. These isozymes showed inhibition profiles with physiologic/non-physiologic anions quite distinct from any other cytosolic (CA I and II) or transmembrane isoforms (e.g., CA IX) investigated earlier. hCA XII has a good affinity for fluoride and bicarbonate but is not inhibited by heavier halides, perchlorate, nitrate, and nitrite. The best hCA XII inhibitors were cyanide (K(I) of 1 microM) and azide (K(I) of 80 microM). hCA XIV was on the other hand weakly inhibited by fluoride and not at all inhibited by perchlorate, but showed good affinity for most other anions investigated here. Chloride and bicarbonate showed K(I)s in the range of 0.75-0.77 mM for this isoform. The best hCA XIV anion inhibitors were sulfate, phenylarsonic, and phenylboronic acid (K(I) in the range of 10-92 microM).
journal_name
Bioorg Med Chem Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
Innocenti A,Vullo D,Pastorek J,Scozzafava A,Pastorekova S,Nishimori I,Supuran CTdoi
10.1016/j.bmcl.2006.12.113subject
Has Abstractpub_date
2007-03-15 00:00:00pages
1532-7issue
6eissn
0960-894Xissn
1464-3405pii
S0960-894X(07)00039-Xjournal_volume
17pub_type
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