Distortions induced in DNA by cis-platinum interstrand adducts

Journal Article · Tue Mar 10 04:00:00 EST 1992 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00124a010· OSTI ID:5640151

Sip, M; Schwartz, A; Vovelle, F; Ptak, M; Leng, M ^[1]

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1. Centre National de la Recherche Scientifique 1A, Orleans (France)

A 22 base pair double-stranded oligonucleotide containing a unique interstrand adduct resulting from chelation of the two guanine residues within the central sequence d(TGCT/AGCA) by a cis-platinum residue has been studied by means of gel electrophoresis, chemical probes, and molecular mechanics. The anomalously slow electrophoretic mobility of the multimers of the platinated and ligated oligomers suggests that the platinated oligonucleotide is bent. The two cytosine residues (complementary to the platinated guanines) are hyperreactive to hydroxylamine, indicating a large exposure of the two bases to the solvent. The adduct does not induce a local denaturation within the flanking sequences since the adenine residues are not reactive with diethyl pyrocarbonate. This is confirmed by the nonreactivity of the complementary T residues with osmium tetraoxide. These results and the molecular mechanics modeling suggest that the interstrand adduct bends the double helix by approximately 55{degree} toward the major groove, that the double helix conserves its average twist angle, and that the distortion induced by the adduct is localized at the platinated sequence d(GC/CG).

• OSTI ID: 5640151
• Journal Information: Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 31:9; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
ADDUCTS
AMINES
AROMATICS
AZAARENES
AZINES
BIOLOGICAL EFFECTS
CYTOSINE
DNA
DNA ADDUCTS
GUANINE
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
MOLECULAR BIOLOGY
NUCLEIC ACIDS
OLIGONUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PLATINUM COMPOUNDS
PURINES
PYRIMIDINES
TRANSITION ELEMENT COMPOUNDS