Abstract
The in vitro binding of an orally active anticancer drug JM216 to metallothionein is firstly investigated in this paper. It is revealed that a redox reaction following a substitution reaction from JM216 with rabbit liver Zn7MT-II is presented. The reaction feature, the metal binding stoichiometry and the oxidation states of platinum and sulfur in the products are studied by UV-visible, chromatography and X-ray photoelectron spectroscopy methods. Parts of MT are oxidized to precipitate products with intra and intermolecular CyS-SCy disulfides linkages. Pt(IV) is reduced to its Pt(II) counterpart. And the reduced Pt(II) replace the metal ions in native MTs. Meanwhile it can also cause the dimerization of MT. Increasing the reaction ratio of JM216 to MT leads to a concomitant increase in the apparent yield of the precipitate and dimeric products and the elevation of the binding stoichiometry of Pt to the protein. Based on the experimental data, the reaction mechanism between JM216 and Zn7MT-II in vitro are discussed.
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References
Baker AD, Betteridge D. 1972 In: Photoelectron Spectroscopy Chemical and Analytical Aspects.
Bongers J, Bell JU, Richardson DE. 1991 Platium (II)-thiolate cluster formation in heptaplatium metallothionein. Inorg Chem 30, 315.
Bongers J, Bell JU, Richardson DE. 1988 Platinum (II) binding to metallothioneins. J Inorg Biochem 34, 55.
Bongers J, Walton G, Bell JU, et al. 1988 Nicromolar protein concentrations and metalloprotein stoichiometries obtained vy inductively coupled plasma atomic emission spectrometric determination of sulfur. Anal Chem 60, 2683.
Buhler RHO, Kagi HR. 1974 In: FEBS Lett 39, 229.
Chen P, Onana P, Shaw CF III. 1996 Characterization of calf live Cu and Zn stoichiometries. Biochem J 317, 389–394.
Comeau RD, Mcdonald KW. 1992 Gram scale purification and preparation of rabbit liver zine metallothionein. Prep Biochem 22, 151–156.
Giandomenico CM, Abrams MJ, Murrer BA, et al. 1995 Carboxylation of kinetically insert platinum (IV) hydroxy complexes. An entree into orally active platium (IV) antitumor agents. Inorg Chem 34, 1015–1021.
Hamer DH. 1986 Metallothionein. Annu Rev Biochem 55, 913–951.
Katrib A. 1980 The reduction of platinum (IV) to platinum (II) by x-ray and argon ion bombardment; evidence from x-ray photoelectron spectroscopy. J Electron Spectros Relat Phenom 18, 275–281.
Lemkuil DC, Nettesheim D, Shaw CF III. et al. 1994 Reaction of Cd7-metallothionein with cis-dichlorodiamminc platinum (II). J Biol Chem 269, 24792.
Loehrer PJ, Einhorm LH. 1984 Cisplatin. Ann Intern Med 100, 704.
Mckeage MJ, Mistry P, Ward J, et al. 1995 Phase I and pharmacological study of an oral platinym complex (JM216) does dependent pharmacokinatic with single does administration. Cancer Chemother Pharmacol 36, 451–457.
Mellish KJ, Kelland LR, Harrap KR. 1993 In vitro platinum drug chemosensitivity of human cervical squamous cell carcinoma cell lines with intrinsic and acquired resistance to cisplatin. Br J Cancer 68, 240.
Nielson KB, Atkin CL, Winge DR. 1985 Distinct metal-binding configuratious in metallothionein. J Inorg Biochem 260, 5342–5348.
Palumaa P, Zerbe O, Vasak M. 1993 Formation and spectroscopic characterization of a novel monomeric cadmium and phosphato-containing form of metallothionein. Biochemistry 32, 2874–2879.
Pattanaik A, Bachowski G, Laib J, et al. 1992 Properties of the reaction of cis-dichloro diammincplatinum (II) with metallothionein. J Biol Chem 267, 16121.
Sadler PJ. 1991 Inorganic chemistry and drug design. Adv Inorg Chem 36, 1–48.
Talman EG, Bruning W, Reedijk AL, et al. 1997 Crystal and molecular structures of asymmetric cis-and trans-platium (II/IV) compounds and their reactions with DNA fragments. Inorg Chem 36, 854–861.
Templeton DM, Cherian MG. 1991 In: Riordan JF, Vallee BL. eds. Methods in Enzymology, Vol. 205, Academic Press New York: 11–25.
Zelazowski AJ, Garvey JS, Hoeschele JD. 1984 The in vivo and in vitro binding of platinum to metallothionein. Arch Biochem Biophys 229, 246.
Zhang BL, Huang H, Tang WX. 1995 Interaction of cis-and trans-Diamminedichloroplaatinum with metallothionein in vivo. J Inorg Biochem 58, 1.
Zhang BL, Tang WX. 1994 Kinetics of the reaction of platinum (II) complexes with metallothionein. J Inorg Biochem 56, 143.
Zhong WQ, Zhang Q, Tang WX, et al. 1997 Interaction of sodium chloroplatinate and iproplatin with metallothionein in vivo. J Inorg Biochem 66, 159–164.
Zhong WQ, Zhang Q, Yan Y, Tang WX. 1997 Reaction of a platinum (IV) complex with native Cd, Zn-metallothionein in vitro. J Inorg Biochem 66, 179–185.
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Xing, B., Zhu, H., Shi, Y. et al. In vitro binding of an orally active platinum antitumor drug, JM216 to metallothionein. Biometals 14, 51–57 (2001). https://doi.org/10.1023/A:1016674704056
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DOI: https://doi.org/10.1023/A:1016674704056