title: Nonaromatic sulfonamide group as an ideal anchor for potent human carbonic anhydrase inhibitors: role of hydrogen-bonding networks in ligand binding and drug design.
abstract: X-ray crystal structures of the adducts of human carbonic anhydrase (hCA) isozyme II with derivatives incorporating a sulfamide or sulfamic acid moiety are reported. The absence of a C-SO(2)NH(2) bond in the first type of compound can be exploited for the design of more potent and selective CA inhibitors. This study also explains why sulfate is a several-orders-of-magnitude weaker CA inhibitor compared to derivatives incorporating sulfonamide/sulfamide moieties.
authors.affiliation: Laboratorio di Chimica Inorganica e Bioinorganica, Università degli Studi di Firenze, Via Gino Capponi 7, I-50121, Florence, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Abbate
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
authors.forename: Andrea
authors.initials: A
authors.lastname: Scozzafava
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Orioli
authors.forename: Milton T
authors.initials: MT
authors.lastname: Stubbs
authors.forename: Gerhard
authors.initials: G
authors.lastname: Klebe
mesh_terms: D024402:Carbonic Anhydrase II / Q000737:chemistry*; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry*; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D006860:Hydrogen Bonding; D007527:Isoenzymes / Q000737:chemistry; D008024:Ligands; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry*; D013451:Sulfonic Acids / Q000737:chemistry
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D008024:Ligands; D013449:Sulfonamides; D013451:Sulfonic Acids; C005741:sulfamic acid; D024402:Carbonic Anhydrase II