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Lack of Z-DNA Conformation in Mitomycin-Modified Polynucleotides Having Inverted Circular Dichroism

Tomasz, Maria and Barton, Jacqueline K. and Magliozzo, Catherine C. and Tucker, David and Lafer, Eileen M. and Stollar, B. David (1983) Lack of Z-DNA Conformation in Mitomycin-Modified Polynucleotides Having Inverted Circular Dichroism. Proceedings of the National Academy of Sciences of the United States of America, 80 (10). pp. 2874-2878. ISSN 0027-8424. http://resolver.caltech.edu/CaltechAUTHORS:TOMpnas83

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Abstract

Poly(dG-dC)· poly(dG-dC) and Micrococcus lysodeikticus DNA were modified by exposure to reductively activated mitomycin C, an antitumor antibiotic. The resulting covalent drug-polynucleotide complexes displayed varying degrees of CD inversions, which are strikingly similar to the inverted spectrum observed with Z-DNA. The following criteria have been used to establish, however, that the inverted CD pattern seen in mitomycin C-polynucleotide complexes does not reflect a Z-DNA conformation. (i) The ethanol-induced transition of poly(dG-dC)· poly(dG-dC) from B to Z conformation is not facilitated but rather is inhibited by mitomycin C modification. This may be due to the presence of crosslinks. (ii) Radioimmunoassay indicated no competition for Z-DNA-specific antibody by any of the mitomycin C-modified polynucleotides. (iii) 31P NMR of the complexes yielded a single relatively narrow resonance, which is inconsistent with the dinucleotide repeat characteristic of Z-DNA. Alternative explanations for the inverted CD pattern include a drug-induced left-handed but non-Z conformational change or the superposition of an induced CD onto the CD of B-DNA due to drug-base electronic interactions. These results illustrate the need for caution in interpreting CD changes alone as an indication of Z-DNA conformation.


Item Type:Article
Additional Information:Copyright © 1983 by the National Academy of Sciences Communicated by Gilbert Stork, January 17, 1983. We thank W. T. Bradner (Bristol Laboratories, Syracuse, NY) for a gift of mitomycin C; R. P. C. Valle for technical assistance with the immunological experiments; and David J. Kaplan (University of Kentucky, Lexington, KY) for his excellent suggestions. This work was supported by PSC-City University of New York Faculty Research Awards (to M.T. and J.K.B.) and grants from the National Institutes of Health (CA 28681 to MT.; GM 32203 to J.K.B.), the Petroleum Research Fund administered by the American Chemical Society (to J.K.B.), and the National Science Foundation (PCM 82-01863 to B.D.S.). The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Subject Keywords:31P NMR, radioimmunoassay, antitumor agent, poly(dG-dC).poly(dG-dC), Micrococcus lysodeikticus DNA
Record Number:CaltechAUTHORS:TOMpnas83
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:TOMpnas83
Alternative URL:http://www.pnas.org/cgi/content/abstract/80/10/2874
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:668
Collection:CaltechAUTHORS
Deposited By: Archive Administrator
Deposited On:13 Sep 2005
Last Modified:26 Dec 2012 08:40

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