Fang Fang, Pan Dong-Qi, Qiu Min-Jie, Liu Ting-Ting, Jiang Min, Wang Qi, Shi Jie-Hua
College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310032, China.
State Key Laboratory Breeding Base of Green Chemistry Synthesis Technology, Zhejiang University of Technology, Hangzhou, 310032, China.
Luminescence. 2016 Sep;31(6):1242-50. doi: 10.1002/bio.3097. Epub 2016 Jan 28.
To further understand the mechanism of action and pharmacokinetics of medroxyprogesterone acetate (MPA), the binding interaction of MPA with bovine serum albumin (BSA) under simulated physiological conditions (pH 7.4) was studied using fluorescence emission spectroscopy, synchronous fluorescence spectroscopy, circular dichroism and molecular docking methods. The experimental results reveal that the fluorescence of BSA quenches due to the formation of MPA-BSA complex. The number of binding sites (n) and the binding constant for MPA-BSA complex are ~1 and 4.6 × 10(3) M(-1) at 310 K, respectively. However, it can be concluded that the binding process of MPA with BSA is spontaneous and the main interaction forces between MPA and BSA are van der Waals force and hydrogen bonding interaction due to the negative values of ΔG(0) , ΔH(0) and ΔS(0) in the binding process of MPA with BSA. MPA prefers binding on the hydrophobic cavity in subdomain IIIA (site II'') of BSA resulting in a slight change in the conformation of BSA, but BSA retaining the α-helix structure. Copyright © 2016 John Wiley & Sons, Ltd.
为进一步了解醋酸甲羟孕酮（MPA）的作用机制和药代动力学，采用荧光发射光谱、同步荧光光谱、圆二色光谱和分子对接方法，研究了MPA在模拟生理条件（pH 7.4）下与牛血清白蛋白（BSA）的结合相互作用。实验结果表明，由于形成了MPA - BSA复合物，BSA的荧光发生猝灭。在310 K时，MPA - BSA复合物的结合位点数（n）和结合常数分别约为1和4.6×10³ M⁻¹。然而，由于MPA与BSA结合过程中ΔG⁰、ΔH⁰和ΔS⁰均为负值，可以得出MPA与BSA的结合过程是自发的，且MPA与BSA之间的主要相互作用力是范德华力和氢键相互作用。MPA倾向于结合在BSA亚结构域IIIA（位点II''）的疏水腔内，导致BSA的构象略有变化，但BSA仍保留α - 螺旋结构。版权所有© 2016约翰威立父子有限公司。
