Monofunctional platinum amine complexes destabilize DNA significantly

Abstract

ϩ with the single-stranded CCTGTCC is significantly faster than that of the trans isomer. The solution structure of the platinumϪDNA 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 platinumϪDNA complex decomposes and the cis-[Pt(NH 3 ) 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.

cis -Diammine(pyridine)chloroplatinum(II), a monofunctional platinum(II) antitumor agent: Uptake, structure, function, and prospects

“…Watson-Crick hydrogen bonding between the base pairs is maintained throughout the dodecamer duplex. The double helix is unwound by Ϸ8°in the vicinity of the platination site, a value in agreement with previous NMR spectroscopic results of a heptamer duplex containing the analogous cis-{Pt(NH 3 ) 2 (4-Me-py)} 2ϩ -dG adduct (16). The pyridine ligand of the cis-{Pt(NH 3 ) 2 (py)} 2ϩ moiety is directed toward the 5Ј end of the platinated strand (Figs.…”

Differences in structure, physiological stability, electrochemistry, cytotoxicity, DNA and protein binding properties between two Ru(III) complexes

“…Cisplatin and other antitumor platinum complexes are found to destabilize the helix due to the intrastrand crosslinks formation [44], and the effect of NAMI-A and two other Ru(III) complexes on DNA melting temperature is reported to be dependent on the ionic strength [42]. Given the fact that the coordination sphere around Ru(III) is more crowded than that around Pt(II), it is difficult for Ru(III) to form intrastrand crosslinks.…”

(N7)-Platination and its effect on (N1)H-acidification in nucleoside phosphate derivatives

“…Quite obviously, steric constraints produced by the various Pt(II) adducts decide predominantly whether or not pairing with C is realized. Thus, while interstrand G,G cross-linking by cis-(NH 3 ) 2 Pt(II) causes the two opposite C bases to become extruded from the DNA double helix, hence base pairing is completely prevented [83,84], monofunctional Pt(II) coordination to G-N7 (by cis-(NH 3 ) 2 (pyridine)Pt(II) [85] or by cis-(NH 3 ) 2 (4-Me-pyridine)Pt(II) [86]) retains the G,C pair, although it is significantly moved toward the major groove. The situation with 1,3-intrastrand adducts of Cisplatin with GXG sequences is in between these two extremes, as one G,C pair is affected relatively little, whereas the other one is completely lost [87].…”