NDLI: Influence of cisplatin intrastrand crosslinking on the conformation, thermal stability, and energetics of a 20-mer DNA duplex.

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Influence of cisplatin intrastrand crosslinking on the conformation, thermal stability, and energetics of a 20-mer DNA duplex.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Dunham, S. U. Poklar, N. Pilch, D. S. Lippard, S. J. Redding, E. A. Breslauer, K. J.
Description	Author Affiliation: Poklar N ( Department of Chemistry, Rutgers-The State University of New Jersey, New Brunswick 08903, USA.);
Abstract	cis-Diamminedichloroplatinum(II) (cisplatin) is a widely used anticancer drug that binds to and crosslinks DNA. The major DNA adduct of the drug results from coordination of two adjacent guanine bases to platinum to form the intrastrand crosslink cis-[Pt(NH3)2[d(GpG)-N7(1), -N7(2)]] (cis-Pt-GG). In the present study, spectroscopic and calorimetric techniques were employed to characterize the influence of this crosslink on the conformation, thermal stability, and energetics of a site-specifically platinated 20-mer DNA duplex. CD spectroscopic and thermal denaturation data revealed that the crosslink alters the structure of the host duplex, consistent with a shift from a B-like to an A-like conformation; lowers its thermal stability by approximately 9 degrees C; and reduces its thermodynamic stability by 6.3 kcal/mol at 25 degrees C, most of which is enthalpic in origin; but it does not alter the two-state melting behavior exhibited by the parent, unmodified duplex, despite the significant crosslink-induced changes noted above. The energetic consequences of the cis-Pt-GG crosslink are discussed in relation to the structural perturbations it induces in DNA and to how these crosslink-induced perturbations might modulate protein binding.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	15
Volume Number	93
Language	English
Publisher	National Academy of Sciences
Publisher Date	1996-10-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cisplatin Pharmacology Cross-Linking Reagents DNA Chemistry Nucleic Acid Conformation Drug Effects Oligodeoxyribonucleotides Calorimetry, Differential Scanning Circular Dichroism Deoxyguanosine Analogs & Derivatives Molecular Sequence Data Nucleic Acid Denaturation Chemical Synthesis Spectrophotometry, Ultraviolet Structure-Activity Relationship Thermodynamics Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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