title: Thermodynamic parameters for the association of fluorinated benzenesulfonamides with bovine carbonic anhydrase II.
abstract: This paper describes a calorimetric study of the association of a series of seven fluorinated benzenesulfonamide ligands (C6H(n)F(5-n)SO2NH2) with bovine carbonic anhydrase II (BCA). Quantitative structure-activity relationships between the free energy, enthalpy, and entropy of binding and pKa and log P of the ligands allowed the evaluation of the thermodynamic parameters in terms of the two independent effects of fluorination on the ligand: its electrostatic potential and its hydrophobicity. The parameters were partitioned to the three different structural interactions between the ligand and BCA: the Zn(II) cofactor-sulfonamide bond (approximately 65% of the free energy of binding), the hydrogen bonds between the ligand and BCA (approximately 10%), and the contacts between the phenyl ring of the ligand and BCA (approximately 25%). Calorimetry revealed that all of the ligands studied bind in a 1:1 stoichiometry with BCA; this result was confirmed by 19F NMR spectroscopy and X-ray crystallography (for complexes with human carbonic anhydrase II).
authors: Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA.
authors: Vijay M
authors: VM
authors: Krishnamurthy
authors: Brooks R
authors: BR
authors: Bohall
authors: Chu-Young
authors: CY
authors: Kim
authors: Demetri T
authors: DT
authors: Moustakas
authors: David W
authors: DW
authors: Christianson
authors: George M
authors: GM
authors: Whitesides
mesh_terms: D000818:Animals; D001665:Binding Sites; D002151:Calorimetry; D024402:Carbonic Anhydrase II / Q000737:chemistry*; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry*; D002417:Cattle; D018360:Crystallography, X-Ray; D015195:Drug Design; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry*; D013816:Thermodynamics; D000096926:Benzenesulfonamides
chemical_list: D024402:Carbonic Anhydrase II; D002257:Carbonic Anhydrase Inhibitors; D006845:Hydrocarbons, Fluorinated; D008024:Ligands; D013449:Sulfonamides; D000096926:Benzenesulfonamides