X-Ray Crystallographic and Kinetic Investigations of 6-Sulfamoyl-Saccharin as a Carbonic Anhydrase Inhibitor

Organic and Biomolecular Chemistry 2015
V. Alterio, M. Tanc, Jekaterīna Ivanova, Raivis Žalubovskis, I. Vozny, S. M. Monti, A. Di Fiore, G. De Simone, C. T. Supuran

6-Sulfamoyl-saccharin was investigated as an inhibitor of 11 α-carbonic anhydrase (CA, EC 4.2.1.1) isoforms of human (h) origin, hCA I-XIV, and X-ray crystallographic data were obtained for its adduct with hCA II, the physiologically dominant isoform. This compound possesses two potential zinc-binding groups, the primary sulfamoyl one and the secondary, acylatedsulfonamide. Saccharin itself binds to the Zn(ii) ion from the CA active site coordinating with this last group, in deprotonated (SO<inf>2</inf>N^-CO) form. Here we explain why 6-sulfamoyl-saccharin, unlike saccharin, binds to the metal ion from the hCA II active site by its primary sulfonamide moiety and not the secondary one as saccharin itself. Our study is useful for shedding new light to the structure-based drug design of isoform-selective CA inhibitors of the sulfonamide type. This journal is

DOI
10.1039/c4ob02648a
Hyperlink
http://pubs.rsc.org/en/Content/ArticleLanding/2015/OB/C4OB02648A#!divAbstract

Alterio, V., Tanc, M., Ivanova, J., Žalubovskis, R., Vozny, I., Monti, S., Di Fiore, A., De Simone, G., Supuran, C. X-Ray Crystallographic and Kinetic Investigations of 6-Sulfamoyl-Saccharin as a Carbonic Anhydrase Inhibitor. Organic and Biomolecular Chemistry, 2015, Vol.13, pp.4064-4069. ISSN 1477-0520. Available from: doi:10.1039/c4ob02648a

Publication language
English (en)