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

Research output: Contribution to journalArticlepeer-review

414 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)412-417
Number of pages6
JournalScience
Volume230
Issue number4724
DOIs
Publication statusPublished - 1985
Externally publishedYes

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'X-ray structure of the major adduct of the anticancer drug cisplatin with DNA: cis-[Pt(NH3)2{d(pGpG)}]'. Together they form a unique fingerprint.

Cite this