应用光谱和分子模拟法研究一种聚酰亚胺聚合物与人免疫球蛋白的相互作用

本文利用荧光猝灭法、红外光谱法及计算机模拟技术研究了一种聚酰亚胺聚合物(2,6-Bis(4-amino-2-trifluoromethyl phenoxy-4’- benzoyl)-pyridine，简称BAFP )与人免疫球蛋白（HIgG）的相互作用。同步荧光的结果定性地说明了BAFP影响水溶液中HIgG二级结构的情况。而判定BAFP影响HIgG二级结构的定量依据来自红外光谱，实验数据表明α螺旋结构的含量相比未加入药物时增加了约2.6～10.2%,，β折叠增大了约13.6～27.7%,，而β转角则减小了约23.8～30.3%。分子模拟的结果显示BAFP与HIgG的键合作用很强，并且有四个氢键在BAFP与HIgG分子的色氨酸Trp 170, 缬氨酸Val 105, 甲硫氨酸Met 139 及天冬酰胺Asn 52之间形成；同时也显示出维持药物与蛋白质的相互作用力主要是疏水作用，这与实验所得到的热力学参数判定作用力的结果相一致（依据范德霍夫公式计算得 与 的值分别为-6.70KJ.mol-1 和 71.93 J.mol-1.K-1）。

Interaction Study of 2,6‐Bis[4‐(4‐amino‐2‐trifluoromethyl phenoxy)benzoyl] Pyridine with Human Immunoglobulin by Optical Spectroscopy and Molecular Modeling

The interaction between human immunoglobulin (HIgG) and BAFP (2,6‐bis4‐(4‐amino‐2‐trifluoromethyl phenoxy)benzoyl] pyridine was studied by fluorescence quenching, Fourier transform infrared (FT‐IR) spectra and molecule modeling. The synchronous fluorescence spectra indicated the information on qualitative changes of the protein secondary structure in the presence of BAFP in aqueous solution. The quantitative alterations of the protein secondary structure were estimated by the evidences from FT‐IR spectra with increases of α helices by about 2.6%–10.2%, increases of β‐sheet structure by about 13.6%–27.7%, and reductions of β‐turn structure by about 23.8%–30.3%. Molecular docking suggests that BAFP can strongly bind to HIgG. There are four hydrogen bond interactions between the drug and the residues Trp 170, Val 105, Met 139 and Asn 52. It was also considered that BAFP bound to HIgG mainly by a hydrophobic interaction, which is in good agreement with the results from the experimental thermodynamic parameters (the enthalpy change ΔH^? and the entropy change ΔS^? were calculated to be ?6.70 kJ·mol^?1 and 71.93 J·mol^?1·K^?1, respectively, according to the Van't Hoff equation).