DNA conformational change produced by the site-specific interstrand cross-link of trans-diamminedichloroplatinum(II).
The DNA distortion produced by the interstrand cross-link of trans-diamminedichloroplatinum-(II) has been described by means of gel electrophoresis, chemical probes, and molecular mechanics modeling. Synthetic double-stranded oligodeoxyribonucleotides of varying lengths (19-22 base pairs) were synthesized that contained a unique site-specific interstrand cross-link within their central sequence d(TGCT)/d(AGCT) between complementary guanine and cytosine residues. We find that the platinated deoxyriboguanosine residue adopts syn conformation. The duplex is distorted on both sides of the cross-link, but the bases are still paired. The distortion introduces some flexibility into the helix. In addition, the double helix is unwound and bent toward the major groove.
Brabec
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V
Centre de Biophysique Moléculaire, CNRS, Orléans, France.
Síp
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M
Leng
M
M
D001483:Base Sequence; D002945:Cisplatin / Q000494:pharmacology*; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D004591:Electrophoresis, Polyacrylamide Gel; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation / Q000187:drug effects*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D013237:Stereoisomerism
D003432:Cross-Linking Reagents; D009838:Oligodeoxyribonucleotides; C034697:transplatin; D004247:DNA; D002945:Cisplatin