X-ray structure of the major adduct of the anticancer drug cisplatin with DNA: cis-[Pt(NH3)2{d(pGpG)}]

Suzanne E. Sherman, Dan Gibson, Andrew H.J. Wang, Stephen J. Lippard

研究成果: 雜誌貢獻文章同行評審

414 引文 斯高帕斯(Scopus)

摘要

Crystals of the adduct of the anticancer drug cis- diamminedichloroplatinum(II), cis-DDP, with d(pGpG), its putative target on DNA in the cancer cell, have been obtained and used in an x-ray crystallographic study to elucidate the molecular structure to atomic resolution. Each of the four crystallographically independent cis-[Pt(NH3) 2{d(pGpG)}] molecules is comprised of a square-planar platinum atom bonded to two ammonia ligands and two N(7) atoms of guanosine nucleosides from the same chain. Base stacking of the two adjacent guanine rings is completely disrupted by coordination to the cis-{Pt(NH3)2} 2+ unit. Comparison of the backbone and deoxyribose ring torsion angles with those found by previous (nuclear magnetic resonance spectroscopy) studies of this adduct in solution demonstrates that the solid state geometry is substantially the same as that in solution. The relevance of these results to the molecular mechanism of action of cis-DDP is discussed.

原文英語
頁(從 - 到)412-417
頁數6
期刊Science
230
發行號4724
DOIs
出版狀態已發佈 - 1985
對外發佈

ASJC Scopus subject areas

  • 多學科

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