Publication Date:
1995-12-15
Description:
The widely used antitumor drug cis-diamminedichloroplatinum(II) (cisplatin or cis-DDP) reacts with DNA, cross-linking two purine residues through the N7 atoms, which reside in the major groove in B-form DNA. The solution structure of the short duplex [d(CAT-AGCTATG)]2 cross-linked at the GC:GC site was determined by nuclear magnetic resonance (NMR). The deoxyguanosine-bridging cis-diammineplatinum(II) lies in the minor groove, and the complementary deoxycytidines are extrahelical. The double helix is locally reversed to a left-handed form, and the helix is unwound and bent toward the minor groove. These findings were independently confirmed by results from a phase-sensitive gel electrophoresis bending assay. The NMR structure differs markedly from previously proposed models but accounts for the chemical reactivity, the unwinding, and the bending of cis-DDP interstrand cross-linked DNA and may be important in the formation and repair of these cross-links in chromatin.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huang, H -- Zhu, L -- Reid, B R -- Drobny, G P -- Hopkins, P B -- GM32681/GM/NIGMS NIH HHS/ -- GM45804/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1995 Dec 15;270(5243):1842-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of Washington, Seattle 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8525382" target="_blank"〉PubMed〈/a〉
Keywords:
Antineoplastic Agents/*pharmacology
;
Base Sequence
;
Cisplatin/*pharmacology
;
DNA/*chemistry/drug effects
;
Magnetic Resonance Spectroscopy
;
Models, Molecular
;
Molecular Sequence Data
;
*Nucleic Acid Conformation
;
Solutions
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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