Binding of [(dien)PtCl]Cl to poly(dG-dC).poly(dG-dC) facilitates the B→Z conformational transition

Henry Michael Ushay, R. M. Santella, J. P. Caradonna, D. Grunberger, S. J. Lippard

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Chlorodiethylenetriamineplatinum(II) chloride, [(dien)ptCl]Cl bound to ≤ 10% of the nucleotide bases of poly(dG-dC)· poly(dG-dC) reduces the amount of ethanol necessary to bring about the B→Z conformational transition in proportion to the amount of platinum complex bound as monitored by CD spectroscopy. The transition may be effected by 25% ethanol with 9.3% of the bases modified and by 36% ethanol with 5.4% of the bases modified. With an unmodified polymer an ethanol concentration of 55-60% is necessary to bring about the transition. The assignment of the Z conformation was supported by P NMR spectroscopy. This covalent modification of the DNA is reversed by treatment with cyanide ion after which the normal amount of ethanol is necessary to achieve the transition. The platinum complex shows no enhanced binding to DNA in the Z versus the B conformation. Between 20 and 33% (saturation binding) modification, [(dien)PtCl]Cl binds cooperatively to the heterocopolymer as judged by CD spectroscopy. At. this high level of modification it is no longer possible to induce the 1 DNA structure with ethanol. When [(dien)PtCl]Cl is bound to preformed (with ethanol) Z DNA at saturating levels the CD spectrum is altered but reverts to the spectrum of highly modified DNA upon removal of ethanol. The antitumor drug cis-diamminedichloroplatinum(II), cis-DDP, binds to poly(dG-dC)·poly(dG-dC) and alters the CD spectrum. It does not facilitate the B→Z conformational change, however, and actually prevents it from happening even at very high ethanol concentrations.

Original languageEnglish (US)
Pages (from-to)3573-3588
Number of pages16
JournalNucleic Acids Research
Volume10
Issue number11
DOIs
StatePublished - Jun 11 1982
Externally publishedYes

Fingerprint

Ethanol
DNA
Spectroscopy
Platinum
Conformation
Necessary
Conformations
Spectrum Analysis
Z-Form DNA
poly(dC-dG)
Cyanides
Nucleotides
Antineoplastic Agents
Cisplatin
Nuclear magnetic resonance spectroscopy
Saturation
Chlorides
Drugs
Polymers
Proportion

ASJC Scopus subject areas

  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Health, Toxicology and Mutagenesis
  • Toxicology
  • Genetics(clinical)
  • Genetics

Cite this

Binding of [(dien)PtCl]Cl to poly(dG-dC).poly(dG-dC) facilitates the B→Z conformational transition. / Ushay, Henry Michael; Santella, R. M.; Caradonna, J. P.; Grunberger, D.; Lippard, S. J.

In: Nucleic Acids Research, Vol. 10, No. 11, 11.06.1982, p. 3573-3588.

Research output: Contribution to journalArticle

Ushay, Henry Michael ; Santella, R. M. ; Caradonna, J. P. ; Grunberger, D. ; Lippard, S. J. / Binding of [(dien)PtCl]Cl to poly(dG-dC).poly(dG-dC) facilitates the B→Z conformational transition. In: Nucleic Acids Research. 1982 ; Vol. 10, No. 11. pp. 3573-3588.
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abstract = "Chlorodiethylenetriamineplatinum(II) chloride, [(dien)ptCl]Cl bound to ≤ 10{\%} of the nucleotide bases of poly(dG-dC)· poly(dG-dC) reduces the amount of ethanol necessary to bring about the B→Z conformational transition in proportion to the amount of platinum complex bound as monitored by CD spectroscopy. The transition may be effected by 25{\%} ethanol with 9.3{\%} of the bases modified and by 36{\%} ethanol with 5.4{\%} of the bases modified. With an unmodified polymer an ethanol concentration of 55-60{\%} is necessary to bring about the transition. The assignment of the Z conformation was supported by P NMR spectroscopy. This covalent modification of the DNA is reversed by treatment with cyanide ion after which the normal amount of ethanol is necessary to achieve the transition. The platinum complex shows no enhanced binding to DNA in the Z versus the B conformation. Between 20 and 33{\%} (saturation binding) modification, [(dien)PtCl]Cl binds cooperatively to the heterocopolymer as judged by CD spectroscopy. At. this high level of modification it is no longer possible to induce the 1 DNA structure with ethanol. When [(dien)PtCl]Cl is bound to preformed (with ethanol) Z DNA at saturating levels the CD spectrum is altered but reverts to the spectrum of highly modified DNA upon removal of ethanol. The antitumor drug cis-diamminedichloroplatinum(II), cis-DDP, binds to poly(dG-dC)·poly(dG-dC) and alters the CD spectrum. It does not facilitate the B→Z conformational change, however, and actually prevents it from happening even at very high ethanol concentrations.",
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