title: Disulfide bond cleavage induced by a platinum(II) methionine complex.
abstract: 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.
authors.affiliation: State Key Laboratory of Coordination Chemistry, Coordination Chemistry Institute, Nanjing University, 210093 Nanjing, PR China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Wei
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Wang
authors.forename: Qin
authors.initials: Q
authors.lastname: Liu
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Mei
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.forename: Zijian
authors.initials: Z
authors.lastname: Guo
mesh_terms: D005978:Glutathione / Q000737:chemistry; D019803:Glutathione Disulfide / Q000737:chemistry*; D007700:Kinetics; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000737:chemistry*
chemical_list: D009944:Organoplatinum Compounds; C510724:platinum(II) methionine dichloride; D005978:Glutathione; D019803:Glutathione Disulfide