Melting of complexes of DNA-cis-DDP in acidic environment

Dalyan, Yeva B.; Haroutiunian, T S; Haroutiunian, Samvel G.; Vardevanyan, P. O.

doi:10.1038/emm.2003.69

Cited by 11 publications

(5 citation statements)

References 10 publications

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“…The melting temperature of the adduct is 42 °C higher than that of the unplatinated DNA, 76 and 34 °C, respectively, indicating the formation of DNA IXLs. The DNA IXLs increase the DNA melting point, in contrast to the behavior of intrastrand cross-links [18]. The increase in melting temperature is similar to that observed previously (38–44 °C) for long-range Pt,Pt-DNA 1,4-IXLs [12, 19].…”

Section: Resultssupporting

confidence: 73%

Structural consequences of a 3′ → 3′ DNA interstrand cross-link by a trinuclear platinum complex: unique formation of two such cross-links in a 10-mer duplex

Tran

Farrell

2009

J Biol Inorg Chem

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Combined multidimensional nuclear magnetic resonance spectroscopy and electrospray mass spectrometry was used to analyze the platinated DNA adduct of the phase II anticancer drug [{trans-PtCl(NH 3 ) 2 } 2 -μ-{trans-Pt(NH 3 ) 2 (NH 2 (CH 2 ) 6 NH 2 ) 2 }](NO 3 ) 4 (BBR3464) with [5′-d (ACG*TATACG*T)-3′] 2 . Two 1,2-interstrand cross-links were formed by concomitant binding of two trinuclear moieties to the oligonucleotide. The four DNA-bound platinum atoms coordinated in the major groove at N7 positions of guanines in the 3′ → 3′ direction and the central platinum unit is expected to lie in the DNA minor groove. This is the first report of such a DNA lesion. The melting temperature of the adduct is 76 °C and is 42 °C higher than that of the unplatinated DNA. The sugar residues of the platinated bases are in the N-type conformation and the G9 nucleoside is in the syn orientation, while the G3 nucleoside appears to retain the anti configuration. The secondary structure of DNA was significantly changed upon cross-linking of the two BBR3464 molecules. Base destacking occurs between A1/C2 and C2/G3 and weakened stacking is seen for the C8/G9 and G9/ T10 bases. The lack of Watson-Crick base pairing is also seen for A1-T10 and C2-G9 base pairs, whereas Watson-Crick base pairs in the central sequence of the DNA (T4 → A7) are well maintained. While DNA repair proteins may "see" different platinated adducts as bulky "lesions", the subtle differences involved in base pairing and stacking, as summarized here, may extend to their role as a substrate for repair enzymes. Thus, differences in protein recognition and repair efficiency among the various interstrand cross-links are likely and a subject worthy of detailed exploration.

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Section: Resultssupporting

confidence: 73%

Structural consequences of a 3′ → 3′ DNA interstrand cross-link by a trinuclear platinum complex: unique formation of two such cross-links in a 10-mer duplex

Tran

Farrell

2009

J Biol Inorg Chem

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“…In the case of long DNAs, there has been no clear correspondence between the distortion of DNA structure induced by platinum compounds and the decrease in thermal stability when measured in a medium with pH~7 [23,35,[41][42][43][44][45][46][47][48][49][50][51][52]. Only cisplatin caused thermal destabilization at any reasonable cation concentration demonstrating qualitative accordance with strong structural distortions [35,[41][42][43][44][45][46][47][48].…”

mentioning

confidence: 82%

“…Only cisplatin caused thermal destabilization at any reasonable cation concentration demonstrating qualitative accordance with strong structural distortions [35,[41][42][43][44][45][46][47][48]. However, the value of destabilization is small.…”

mentioning

confidence: 86%

“…Of the three compounds, only cisplatin decreased melting temperature of long DNAs [35,[41][42][43][44][45][46][47][48]. For [Pt(dien)Cl]Cl and transplatin, the value of δT m is positive at low [Na + ] and tends to zero at [Na + ]= 0.1-0.2 M. Even more surprising is the observation that [Pt(dien)Cl]Cl and transplatin complexes with long DNAs demonstrate the same melting behavior in neutral medium in spite of different final adducts [23,35].…”

Section: Thermal Stability Of Short and Long Platinated Dnas In Neutrmentioning

confidence: 99%

“…It allows the simultaneous measurement of parameters characterizing their rate of formation and influence on DNA thermal stability. In all prior work, only the net effect of the final modifications was measured for long DNAs [23,35,[41][42][43][44][45][46][47][48][49][50][51][52].…”

mentioning

confidence: 99%

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