Thermodynamic parameters for the association of fluorinated benzenesulfonamides with bovine carbonic anhydrase II
Thermodynamic parameters for the association of fluorinated benzenesulfonamides with bovine carbonic anhydrase II
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DOI：
10.1002/asia.200600360
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发表时间：
2007-01-01
影响因子：
4.1
通讯作者：
Whitesides, George M.
中科院分区：
文献类型：
--
作者：
Krishnamurthy, Vijay M.;Bohall, Brooks R.;Whitesides, George M.
用量热法研究了七种含氟苯磺酰胺配体（C_6H_nF_5-nSO_2NH_2）与牛碳酸酐酶Ⅱ（BCA）的缔合作用。定量的结构活性之间的关系的自由能，焓，和熵的结合和pK（a）和logP的配体允许的热力学参数的评价方面的两个独立的影响的配体上的静电势和疏水性。这些参数被分配到三个不同的结构之间的相互作用的配体和BCA：锌-II辅因子-磺酰胺键（约65%的结合自由能），配体和BCA之间的氢键（约10%），和配体和BCA的苯环之间的接触（约25%）。量热法显示，所有研究的配体与BCA以1：1的化学计量结合;这一结果通过（FNMR）-F-19光谱和X射线晶体学（对于与人碳酸酐酶II的复合物）证实。
This paper describes a calorimetric study of the association of a series of seven fluorinated benzenesulfonamide ligands (C6HnF5-nSO2NH2) with bovine carbonic anhydrase II (BCA). Quantitative structure-activity relationships between the free energy, enthalpy, and entropy of binding and pK(a) and logP 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 ( approximate to 65% of the free energy of binding), the hydrogen bonds between the ligand and BCA (approximate to 10%), and the contacts between the phenyl ring of the ligand and BCA (approximate to 25%). Calorimetry revealed that all of the ligands studied bind in a 1:1 stoichiometry with BCA; this result was confirmed by (FNMR)-F-19 spectroscopy and X-ray crystallography (for complexes with human carbonic anhydrase II).