Momburg R, Bourdeaux M, Sarrazin M, Chauvet M, Briand C
Laboratory of Pharmaceutical Physics, Faculty of Pharmacy, Marseille, France.
J Pharm Pharmacol. 1987 Sep;39(9):691-7. doi: 10.1111/j.2042-7158.1987.tb06971.x.
The interaction of cis-dichlorodiammineplatinum (II) (cisplatin) with human serum albumin (HSA), dissolved in phosphate buffer with or without sodium chloride (0.1 M) has been examined at pH 7.4 and mu = 0.154. Equal volumes of cisplatin and HSA solutions were incubated at 37 degrees C for various times and filterable platinum concentrations versus time measured by flameless atomic absorption spectrophotometry. Binding kinetics differed depending on the buffer solutions used and on the time elapsing between cisplatin dissolution and outset of incubation with HSA. Experimental data were fitted to a theoretical equation used to calculate the number of nucleophilic sites per HSA molecule. Titrations of the HSA sulphydryl group content before and after incubation with a cisplatin solution were made, from which it was shown that the lone SH-group of the HSA macromolecule is involved in cisplatin binding. We also studied HSA's sensitivity towards denaturing agents when it was complexed with cisplatin. This sensitivity was decreased upon cisplatin binding. Also, the binding capacities of HSA and the HSA-Pt(II) complex to both tryptophan and warfarin were compared to determine the possible influence of cisplatin upon the binding to HSA of other drugs; this influence was negligible.
在pH值为7.4、离子强度μ = 0.154的条件下，研究了顺式二氯二氨铂（II）（顺铂）与溶解于含或不含氯化钠（0.1 M）的磷酸盐缓冲液中的人血清白蛋白（HSA）之间的相互作用。将等体积的顺铂溶液和HSA溶液在37℃下孵育不同时间，然后通过无火焰原子吸收分光光度法测量可过滤的铂浓度随时间的变化。结合动力学因所用缓冲溶液以及顺铂溶解与开始与HSA孵育之间的时间间隔而异。将实验数据拟合到一个理论方程，用于计算每个HSA分子中的亲核位点数量。对与顺铂溶液孵育前后的HSA巯基含量进行滴定，结果表明HSA大分子的单个SH基团参与了顺铂的结合。我们还研究了与顺铂络合时HSA对变性剂的敏感性。顺铂结合后，这种敏感性降低。此外，比较了HSA和HSA-Pt（II）络合物对色氨酸和华法林的结合能力，以确定顺铂对其他药物与HSA结合的可能影响；这种影响可以忽略不计。
