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ID: ALA1155543

Journal: Bioorg Med Chem Lett

Title: Carbonic anhydrase inhibitors: crystallographic and solution binding studies for the interaction of a boron-containing aromatic sulfamide with mammalian isoforms I-XV.

Authors: Di Fiore A, Monti SM, Innocenti A, Winum JY, De Simone G, Supuran CT.

Abstract: We investigated the inhibition of carbonic anhydrase (CA, EC 4.2.1.1) isoforms I-XV with 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylsulfamide and other simple or sugar sulfamides, a class of less investigated CA inhibitors (CAIs). The crystal structure of the adduct of hCA II with the boron-substituted sulfamide shows the organic scaffold of this compound bound in the hydrophilic half of the active site where it makes a large number of van der Waals contacts with Ile91, Gln92, Val121, Phe131, Leu198, and Thr200. The data here reported provide further insights into sulfamide binding mechanism confirming that this zinc-binding group could be usefully exploited for obtaining new potent and selective CAIs.

CiteXplore: 20472429

DOI: 10.1016/j.bmcl.2010.04.114