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DNA INTERSTRAND CROSS-LINKS OF TRANS-DIAMMINEDICHLOROPLATINUM(II) ARE PREFERENTIALLY FORMED BETWEEN GUANINE AND COMPLEMENTARY CYTOSINE RESIDUES
被引:267
作者:
BRABEC, V
[1
]
LENG, M
[1
]
机构:
[1] CZECHOSLOVAK ACAD SCI, INST BIOPHYS, CS-61265 BRNO, CZECHOSLOVAKIA
来源:
关键词:
SP6 AND T7 RNA POLYMERASES;
TRANSCRIPTION MAPPING;
DIMETHYL SULFATE;
D O I:
10.1073/pnas.90.11.5345
中图分类号:
O [数理科学和化学];
P [天文学、地球科学];
Q [生物科学];
N [自然科学总论];
学科分类号:
07 ;
0710 ;
09 ;
摘要:
Bases in the opposite strands of DNA cross-linked by clinically ineffective trans-diamminedichloroplatinum(II) {trans-[Pt(NH3)2Cl2]} have been identified by means of three experimental approaches. These include HPLC analysis of enzymatic digests of synthetic oligonucleotide duplexes containing the interstrand cross-link, footprinting experiments on the interstrand cross-linked oligonucleotide duplexes, and termination of the duplex transcription on trans-[Pt(NH3)2Cl2]-treated fragments of plasmid DNA. The results reveal that deoxyguanine and complementary deoxycytosine residues are preferential binding sites of trans-[Pt(NH3)2Cl2] in the inter-strand adducts. The interstrand cross-linking reaction was studied by means of gel electrophoresis for the cis and trans isomers. The rate of formation of interstrand cross-links was lower for the trans isomer; however, trans-[Pt(NH3)2Cl2] formed about twice the amount of interstrand cross-links as compared with the cis isomer after 48 hr. The present results are suggested to be relevant to differences in clinical activity of the two platinum(II) isomers.
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页码:5345 / 5349
页数:5
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