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L-甲硫氨酸和5'-鸟苷酸对铂(II)配合物的竞争反应。

Competitive reactions of L-methionine and 5'-GMP towards platinum (II) complexes.

作者信息

Soldatović Tanja, Canović Predrag, Canović Dragan, Bugarcić Zivadin D

机构信息

University of Kragujevac, Faculty of Science, Department of Chemistry; R. Domanovic'a 12, P. O. Box 60, 34000 Kragujevac, Serbia.

出版信息

Med Chem. 2005 Nov;1(6):547-61. doi: 10.2174/157340605774598117.

DOI:10.2174/157340605774598117
PMID:16787339
Abstract

The complex-formation reactions of the platinum(II) complexes, [Pt(dien)H2O]2+, [PtCl(dien)]+ and [PtBr(dien)]+ (dien is diethylenetriamine) with some biologically relevant ligands such as inosine (INO), inosine-5'-monophosphate (5'-IMP), guanosine-5'-monophosphate (5'-GMP), glutathione (GSH) and L-methionine (S-meth), were studied by UV-Vis (UV-Visible) spectrophotometry and 1H NMR spectroscopy. Reactions of the [PtCl(dien)]+ with L-methionine were studied in the presence and absence of 5'-GMP. The rate constants clearly showed a kinetic preference toward L-methionine. However, competitive reactions of [PtCl(dien)]+ with L-methionine and 5'-GMP demonstrated initially rapid formation of [Pt(dien)(S-meth)]2+ followed by displacement of L-methionine by 5'-GMP. In the later stages the concentration of [Pt(dien)(N7-GMP )]2+ is predominant. The results are analyzed in reference to the anti-tumour activity of Pt(II) complexes.

摘要

通过紫外可见分光光度法和核磁共振氢谱研究了铂(II)配合物[Pt(dien)H2O]2+、[PtCl(dien)]+和[PtBr(dien)]+(dien为二乙烯三胺)与一些具有生物学相关性的配体,如肌苷(INO)、5'-肌苷单磷酸(5'-IMP)、5'-鸟苷单磷酸(5'-GMP)、谷胱甘肽(GSH)和L-甲硫氨酸(S-meth)的络合反应。在有和没有5'-GMP的情况下研究了[PtCl(dien)]+与L-甲硫氨酸的反应。速率常数清楚地表明了对L-甲硫氨酸的动力学偏好。然而,[PtCl(dien)]+与L-甲硫氨酸和5'-GMP的竞争反应表明,最初快速形成[Pt(dien)(S-meth)]2+,随后L-甲硫氨酸被5'-GMP取代。在后期阶段,[Pt(dien)(N7-GMP )]2+的浓度占主导。结合铂(II)配合物的抗肿瘤活性对结果进行了分析。

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