Chemical probes of the conformation of DNA modified by cis-diamminedichloroplatinum(II)
- Centre de Biophysique Moleculaire, Orleans (France)
The purpose of this work was to analyze at the nucleotide level the distortions induced by the binding of cis-diamminedichloroplatinum(II) (cis-DDP) to DNA by means of chemical probes. In order to test the chemical probes, experiments were first carried out on two platinated oligonucleotides. It has been verified by circular dichroism and gel electrophoresis that the binding of cis-DDP to an AG or to a GTG site within a double-stranded oligonucleotide distorts the double helix. The reactivity of the oligonucleotide platinated at the GTG site with chloroacetaldehyde, diethyl pyrocarbonate, and osmium tetraoxide, respectively, suggests a local denaturation of the double helix. The 5'G residue and the T residue within the adduct are no longer paired, while the 3'G residue is paired. The double helix is more distorted (but not denatured) at the 5' side of the adduct than at the 3' side. The reactivities of the chemical probes with six platinated DNA restriction fragments show that even at a relatively high level of platination only a few base pairs are unpaired but the double helix is largely distorted. No local denaturation has been detected at the GG sites separated from the nearest GG or AG sites by at least three base pairs. The AG sites separated from the nearest AG or GG sites by at least three base pairs do not denature the double helix locally when they are in the sequences puAG/pyTC. It is suggested that the distortion within these sequences is induced by adducts located further away along the DNA fragments, these sequences not being the major sites for the binding of cis-DDP.
- OSTI ID:
- 5645327
- Journal Information:
- Biochemistry; (USA), Vol. 28:4; ISSN 0006-2960
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
DNA
CONFORMATIONAL CHANGES
PLATINUM COMPOUNDS
BIOLOGICAL EFFECTS
ABSORPTION SPECTRA
ADENINES
ATP
DICHROISM
DNA ADDUCTS
GUANINE
OLIGONUCLEOTIDES
PHOSPHORUS 32
ADDUCTS
AMINES
ANTIMETABOLITES
AROMATICS
AZAARENES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
DAYS LIVING RADIOISOTOPES
DRUGS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
ISOTOPES
LIGHT NUCLEI
NUCLEI
NUCLEIC ACIDS
NUCLEOTIDES
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHOSPHORUS ISOTOPES
PURINES
RADIOISOTOPES
SPECTRA
TRANSITION ELEMENT COMPOUNDS
560300* - Chemicals Metabolism & Toxicology