KINETICS OF THE REACTION OF PLATINUM(II) COMPLEXES WITH METALLOTHIONEIN

被引:16
作者
ZHANG, BL
TANG, WX
机构
[1] State Key Laboratory of Coordination Chemistry, Coordination Chemistry Institute, Nanjing University, Nanjing
关键词
D O I
10.1016/0162-0134(94)85001-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Properties of the reactions of cis-dichlorodiammineplatinum (II)(cis-DDP) and related complexes with rabbit liver zinc-+ or apo-thionein have been investigated. A similar product containing 7.0 mol Pt(II) per mol of protein is obtained when excess cis-DDP or other Pt(II) complexes were reacted with Zn(7)MT(2) at neutral pH. The kinetics of reactions are triphasic as monitored by the formation of Pt-thiolate. The pseudo first-order rate constants k(I), k(II), and k(III) corresponding to three rate-limiting steps are determined, respectively. The results show that the first rate step is sensitive to the nature of the ligands occupying the other two coordination sites in diammine-Pt(II), whereas k(II) and k(III) do not change markedly toward different conditions. Significantly, trans-DDP has a strong kinetic preference for MT compared with cis-DDP. A mechanism for these reactions is proposed in which all of the hydrolysis species of platinum(II) complexes react directly with metallothionein followed by the loss of ammine ligands as the product is formed. The obtained kinetic data are discussed in relation to the antitumor activity and toxicity of platinum(II) complexes.
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页码:143 / 153
页数:11
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共 29 条
[11]  
ENDRESEN L, 1984, ACTA PHARMACOL TOX, V55, P183
[12]   CRYSTAL-STRUCTURE OF CD,ZN METALLOTHIONEIN [J].
FUREY, WF ;
ROBBINS, AH ;
CLANCY, LL ;
WINGE, DR ;
WANG, BC ;
STOUT, CD .
SCIENCE, 1986, 231 (4739) :704-710
[13]   SPECTROSCOPIC PROPERTIES OF THE COBALT(II)-SUBSTITUTED ALPHA-FRAGMENT OF RABBIT LIVER METALLOTHIONEIN [J].
GOOD, M ;
VASAK, M .
BIOCHEMISTRY, 1986, 25 (11) :3328-3334
[14]  
HAMADA T, 1989, JPN J CANC CHEMOTHER, V16, P3587
[15]  
ISMAIL IM, 1983, ACS SYM SER, V209, P171
[16]   OVEREXPRESSION OF METALLOTHIONEIN CONFERS RESISTANCE TO ANTICANCER DRUGS [J].
KELLEY, SL ;
BASU, A ;
TEICHER, BA ;
HACKER, MP ;
HAMER, DH ;
LAZO, JS .
SCIENCE, 1988, 241 (4874) :1813-1815
[17]  
KLEINBERG J, 1963, INORGANIC SYNTHESES, V7, P240
[18]   BINDING OF CIS-DICHLORODIAMMINE PLATINUM(II) TO METALLOTHIONEIN IN EHRLICH CELLS [J].
KRAKER, A ;
SCHMIDT, J ;
KREZOSKI, S ;
PETERING, DH .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1985, 130 (02) :786-792
[19]   NATURE OF CIS AMINE PD(II) AND ANTITUMOR CIS AMINE PT(II) COMPLEXES IN AQUEOUS-SOLUTIONS [J].
LIM, MC ;
MARTIN, RB .
JOURNAL OF INORGANIC & NUCLEAR CHEMISTRY, 1976, 38 (10) :1911-1914
[20]  
MONIA BP, 1987, MOL PHARMACOL, V31, P21