TY - JOUR
T1 - Thermodynamic parameters for the association of fluorinated benzenesulfonamides with bovine carbonic anhydrase II
AU - Krishnamurthy, Vijay M.
AU - Bohall, Brooks R.
AU - Kim, Chu Young
AU - Moustakas, Demetri T.
AU - Christianson, David W.
AU - Whitesides, George M.
PY - 2007
Y1 - 2007
N2 - This paper describes a calorimetric study of the association of a series of seven fluorinated benzenesulfonamide ligands (C6HnF 5-nSO2NH2) 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 hydrophohicity. The parameters were partitioned to the three different structural interactions between the ligand and BCA: the ZnII cofactor-sulfonamide bond (≈ 65% of the free energy of binding), the hydrogen bonds between the ligand and BCA (≈10%), and the contacts between the phenyl ring of the ligand and BCA (≈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).
AB - This paper describes a calorimetric study of the association of a series of seven fluorinated benzenesulfonamide ligands (C6HnF 5-nSO2NH2) 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 hydrophohicity. The parameters were partitioned to the three different structural interactions between the ligand and BCA: the ZnII cofactor-sulfonamide bond (≈ 65% of the free energy of binding), the hydrogen bonds between the ligand and BCA (≈10%), and the contacts between the phenyl ring of the ligand and BCA (≈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).
KW - Calorimetry
KW - Fluorinated ligands
KW - Ligand design
KW - Rational drug design
KW - Structure-activity relationships
UR - https://www.scopus.com/pages/publications/33846320455
UR - https://www.scopus.com/pages/publications/33846320455#tab=citedBy
U2 - 10.1002/asia.200600360
DO - 10.1002/asia.200600360
M3 - Article
C2 - 17441142
AN - SCOPUS:33846320455
SN - 1861-4728
VL - 2
SP - 94
EP - 105
JO - Chemistry - An Asian Journal
JF - Chemistry - An Asian Journal
IS - 1
ER -