Dinuclear platinum complexes form a novel intrastrand adduct with d(GpG), an anti-syn conformation of the macrochelate as observed by NMR and molecular modeling

被引:43
作者
Qu, Y
Bloemink, MJ
Reedijk, J
Hambley, TW
Farrell, N
机构
[1] VIRGINIA COMMONWEALTH UNIV, DEPT CHEM, RICHMOND, VA 23284 USA
[2] LEIDEN UNIV, LEIDEN INST CHEM, NL-2300 RA LEIDEN, NETHERLANDS
[3] UNIV SYDNEY, DEPT INORGAN CHEM, SYDNEY, NSW 2006, AUSTRALIA
关键词
D O I
10.1021/ja961823k
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Dinuclear platinum complexes form a unique array of DNA adducts including (Pt,Pt) interstrand and (Pt,Pt) intrastrand cross-links. A (Pt,Pt) intrastrand adduct between two adjacent guanines is the structural analog of the major adduct formed by cis-DDP. In this study, we examined the kinetics of formation and structure of the (Pt,Pt) intrastrand adduct by following the interaction of [{trans-PtCl(NH3)(2)}(2){mu-H2N(CH2)(n)NH2}](2+) (1,1/t,t, n = 2-6) with d(GpG) using NMR spectroscopy and by molecular modeling. Initial coordination, to either the 5'-G or the 3'-G, is relatively fast compared to the second binding step, ring closure to the macrochelate adduct (i.e., [1,1/t,t]-d(GpG)-N7(1),N7(2)). The rate of ring closure depends on the chain length of the diamine linker. Complexes linked by a longer diamine chain (n = 4-6) react faster and produce a higher yield of macrochelate compared to the shorter n = 2, 3 diamine linkers. The structure of the (Pt,Pt) intrastrand adduct is significantly different from the cis-DDP-d(GpG) chelate. The major difference is the presence of a syn-orientated G base (observed for 1,1/t,t-(GpG) macrochelates of n = 3 and n = 6). For the macrochelate of [1,1/t,t, n = 3], i.e., [{trans-PtCl(NH3)(2)}(2){mu-H2N(CH2)(3)NH2}]{d(GpG)-N7(1),N7(2)}, the sugar conformation of the 5'-G (G1) is 28% S, whereas for 3'-G (G2) this value is much higher (69% S). In the corresponding n = 6 macrochelate these values are 55% S and 30% S for G(1) and G(2), respectively. The orientation of the two G bases in the [1,1/t,t]-d(GpG) chelates is best described as tectonic or ''stepped head-to-head''. The structure helps explain the flexible bending in DNA induced by the dinuclear platinum complexes in contrast to the rigid directed bend into the major groove caused by cis-DDP.
引用
收藏
页码:9307 / 9313
页数:7
相关论文
共 71 条
[1]   CONFORMATION OF PT(DIEN)[D(APGPA)-N7(2)] IN THE SOLID-STATE AND IN AQUEOUS-SOLUTION, AS DETERMINED WITH SINGLE-CRYSTAL X-RAY-DIFFRACTION AND HIGH-RESOLUTION NMR-SPECTROSCOPY IN SOLUTION [J].
ADMIRAAL, G ;
ALINK, M ;
ALTONA, C ;
DIJT, FJ ;
VANGARDEREN, CJ ;
DEGRAAFF, RAG ;
REEDIJK, J .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1992, 114 (03) :930-938
[2]   INTRASTRAND BIS(GUANINE) CHELATION OF D(CPGPG) TO CISPLATINUM - AN X-RAY SINGLE-CRYSTAL STRUCTURE-ANALYSIS [J].
ADMIRAAL, G ;
VANDERVEER, JL ;
DEGRAAFF, RAG ;
DENHARTOG, JHJ ;
REEDIJK, J .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1987, 109 (02) :592-594
[3]  
ALTONA C, 1982, RECL TRAV CHIM PAY B, V101, P413
[4]  
[Anonymous], HYP
[5]   THE DINUCLEAR COMPLEX [(TRANS-PTCL(NH3)2)2(MU-H2N(CH2)6NH2)]CL2 FORMS A UNIQUE MACROCHELATE INTRASTRAND CROSS-LINK WITH D(GPG) [J].
BLOEMINK, MJ ;
REEDIJK, J ;
FARRELL, N ;
QU, Y ;
STETSENKO, AI .
JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS, 1992, (14) :1002-1003
[6]  
Bloemink MJ, 1996, MET IONS BIOL SYST, V32, P641
[7]   CONFORMATIONAL DIFFERENCES BETWEEN THE ADDUCTS OF CIS-DDP AND TRANS-DDP WITH THE TRINUCLEOTIDE D(GPTPG) - A H-1 AND (31)NMR INVESTIGATION [J].
BOOGAARD, N ;
ALTONA, C ;
REEDIJK, J .
JOURNAL OF INORGANIC BIOCHEMISTRY, 1993, 49 (02) :129-147
[9]   INTERACTION OF CIS-[PT(NH3)2(H2O)2](NO3)2 WITH RIBOSE DINUCLEOSIDE MONOPHOSPHATES [J].
CHOTTARD, JC ;
GIRAULT, JP ;
CHOTTARD, G ;
LALLEMAND, JY ;
MANSUY, D .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1980, 102 (17) :5565-5572
[10]  
CHRISTIAN MC, 1992, SEMIN ONCOL, V19, P720