Monofunctional platinum amine complexes destabilize DNA significantly

Cornelia Bauer, Tal Peleg-Shulman, Dan Gibson, Andrew H.J. Wang

研究成果: 雜誌貢獻文章同行評審

39 引文 斯高帕斯(Scopus)

摘要

Both cis-[Pt(NH3)2(4-Me-Py)Cl]+ and trans-[Pt(NH3)2(4-Me-Py)Cl]+ bind DNA covalently at the N7 site of guanine residues forming mono-dentate adducts. However, like cisplatin and transplatin, only the cis isomer has anti-cancer activity, whereas the trans-isomer does not. In order to understand the molecular basis of the different activities associated with cis-[Pt(NH3)2(4-Me-Py)Cl]+ and trans-[Pt(NH3)2(4-Me-Py)Cl]+, the interactions of these two platinum compounds with the DNA heptamer CCTG*TCC:GGACAGG duplex (G* is the platinated guanine) have been examined. The reaction rate of cis-[Pt(NH3)2(4-Me-Py)Cl]+ with the single-stranded CCTGTCC is significantly faster than that of the trans isomer. The solution structure of the platinum-DNA adducts has been studied by two-dimensional NMR spectroscopy. Both the cis-platinum adducts and the trans-platinum adducts destabilize the DNA duplex significantly. The melting temperature (T(m)) of the platinated heptamer duplex is estimated to be 10°C lower than for the unplatinated duplex by NMR. At 2°C, the base pairs located on the 5' side of the oligonucleotide, beyond the platinum lesion site, are disrupted. Over time, the platinum-DNA complex decomposes and the cis-[Pt(NH3)2(4-Me-Py)] platinum complex is gradually detached from DNA. No interstrand crosslinking is observed. The biological implications of the structural studies are discussed.

原文英語
頁(從 - 到)253-260
頁數8
期刊European Journal of Biochemistry
256
發行號2
DOIs
出版狀態已發佈 - 9月 1 1998
對外發佈

ASJC Scopus subject areas

  • 生物化學

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