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首页> 外文期刊>Journal of Inorganic Biochemistry: An Interdisciplinary Journal >Effect of cis-, trans-diamminedichloroplatinum(II) and DBP on human serum albumin
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Effect of cis-, trans-diamminedichloroplatinum(II) and DBP on human serum albumin

机译：顺式，反式-二甲基二氯铂（DB）和DBP对人血清白蛋白的影响

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Both isomers of diamminedichloroplatinum(II) bind to albumin and induce the formation of the albumin dimer (MW approx 140kDa). The trans isomer exhibits a much greater tendency to induce a protein dimerization than the cis isomer. Under similar experimental conditions, the phosphonic derivative of diammineplatinum(II) (DBP) does not induce any dimer formation. The amount of bound complex per mol of human serum albumin (HSA, for an incubation time of 7 days) was found to be 6, 10.5 and 1 mol for cis-, trans-DDP and DBP, respectively. The relative fluorescence intensity of platinum-bound HSA decreases to about 55% for cis-DDP, 45% for trans-DDP and to 85% for DBP when compared to the complex-free protein, suggesting that the binding occurs in the proximity of the Trp214 residue. The structural studies (CD) have shown that only DDP-isomers cause the distinct modification of HSA native structure (#alpha#-helical content). Pt(II) complexes binding to HSA affect the affinity of HSA towards heme and bilirubin. High excess of DDP prevents the heme and bilirubin binding, while DBP affects this binding much less effectively due to the low amount of the protein-bound complex. Reactions of platinum complexes with albumin are believed to play an important role in the metabolism of this anticancer drug. The minor effect of DBP on HSA may indicate that the toxicity of the phosphonate analog is much lower than toxicities of DDP isomers, most likely due to kinetic reasons.
机译：diamminedichloroplatinum（II）的两个异构体都结合白蛋白并诱导形成白蛋白二聚体（分子量约为140kDa）。与顺式异构体相比，反式异构体表现出更大的诱导蛋白质二聚化的趋势。在相似的实验条件下，二氨合铂（II）（DBP）的膦酸酯衍生物不会诱导任何二聚体形成。发现每摩尔人血清白蛋白（HSA，7天的孵育时间）结合复合物的量分别为顺式，反式-DDP和DBP分别为6、10.5和1摩尔。与不含复合物的蛋白质相比，与铂结合的HSA的相对荧光强度对于顺式DDP降低至约55％，对于反式DDP降低至45％，对于DBP降低至85％，这表明结合发生在结合蛋白附近。 Trp214残基。结构研究（CD）已显示，只有DDP异构体会引起HSA天然结构（＃alpha＃-螺旋含量）的明显改变。与HSA结合的Pt（II）复合物影响HSA对血红素和胆红素的亲和力。过量的DDP阻止了血红素和胆红素的结合，而DBP由于蛋白质结合的复合物的量少，因此对这种结合的影响要小得多。铂络合物与白蛋白的反应被认为在该抗癌药的代谢中起重要作用。 DBP对HSA的较小影响可能表明，膦酸酯类似物的毒性远低于DDP异构体的毒性，这很可能是由于动力学原因。

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