Wei Haiying, Wang Xiaoyong, Liu Qin, Mei Yuhua, Lu Yi, Guo Zijian
State Key Laboratory of Coordination Chemistry, Coordination Chemistry Institute, Nanjing University, 210093 Nanjing, PR China.
Inorg Chem. 2005 Aug 22;44(17):6077-81. doi: 10.1021/ic050285m.
The cleavage of a disulfide bond and the redox equilibrium of thiol/disulfide are strongly related to the levels of glutathione (GSH)/oxidized glutathione (GSSG) or mixed disulfides in vivo. In this work, the cleavage of a disulfide bond in GSSG induced by a platinum(II) complex [Pt(Met)Cl2] (where Met = methionine) was studied and the cleavage fragments or their platinated adducts were identified by means of electrospray mass spectrometry, high-performance liquid chromatography, and ultraviolet techniques. The second-order rate constant for the reaction between [Pt(Met)Cl2] and GSSG was determined to be 0.4 M(-1) s(-1) at 310 K and pH 7.4, which is 100- and 12-fold faster than those of cisplatin and its monoaqua species, respectively. Different complexes were formed in the reaction of [Pt(Met)Cl2] with GSSG, mainly mono- and dinuclear platinum complexes with the cleavage fragments of GSSG. This study demonstrated that [Pt(Met)Cl2] can promote the cleavage of disulfide bonds. The mechanistic insight obtained from this study may provide a deeper understanding on the potential involvement of platinum complexes in the intracellular GSH/GSSG systems.
二硫键的断裂以及硫醇/二硫键的氧化还原平衡与体内谷胱甘肽（GSH）/氧化型谷胱甘肽（GSSG）或混合二硫键的水平密切相关。在本研究中，对铂（II）配合物[Pt(Met)Cl2]（其中Met = 甲硫氨酸）诱导的GSSG中二硫键的断裂进行了研究，并通过电喷雾质谱、高效液相色谱和紫外技术鉴定了断裂片段或其铂化加合物。在310 K和pH 7.4条件下，[Pt(Met)Cl2]与GSSG反应的二级速率常数被测定为0.4 M(-1) s(-1)，分别比顺铂及其一水合物物种快100倍和12倍。[Pt(Met)Cl2]与GSSG反应形成了不同的配合物，主要是与GSSG断裂片段形成的单核和双核铂配合物。该研究表明，[Pt(Met)Cl2]可以促进二硫键的断裂。从本研究中获得的机理见解可能有助于更深入地理解铂配合物在细胞内GSH/GSSG系统中的潜在作用。
