A Caltech Library Service

Solution conformation of the major adduct between the carcinogen (+)-anti-benzo[ɑ]pyrene diol epoxide and DNA

Cosman, Monique and de los Santos, Carlos and Fiala, Radovan and Hingerty, Brian E. and Singh, Suresh B. and Ibanez, Victor and Margulis, Leonid A. and Live, David and Geacintov, Nicholas E. and Broyde, Suse and Patel, Dinshaw J. (1992) Solution conformation of the major adduct between the carcinogen (+)-anti-benzo[ɑ]pyrene diol epoxide and DNA. Proceedings of the National Academy of Sciences of the United States of America, 89 (5). pp. 1914-1918. ISSN 0027-8424. PMCID PMC48564. doi:10.1073/pnas.89.5.1914.

PDF - Published Version
See Usage Policy.


Use this Persistent URL to link to this item:


We have synthesized, separated, and purified ≈10 mg of a deoxyundecanucleotide duplex containing a single centrally positioned covalent adduct between (+)-anti-benzo[a]pyrene (BP) diol epoxide and the exocyclic amino group of guanosine. Excellent proton NMR spectra are observed for the (+)-trans-anti-BP diol epoxide-N^2-dG adduct positioned opposite dC and flanked by G.C pairs in the d[C1-C2-A3-T4-C5-(BP)G6-C7-T8-A9-C10-C11].d[12- G13-T14-A15-G16-C17-G18-A19-T20-G 21-G22] duplex +ADdesignated (BP)G.C 11-mer+BD. We have determined the solution structure centered about the BP covalent adduct site in the (BP)G.C 11-mer duplex by incorporating intramolecular and intermolecular proton-proton distance bounds deduced from the NMR data sets as constraints in energy minimization computations. The BP ring is positioned in the minor groove and directed toward the 5' end of the modified strand. One face of the BP ring of (BP)G6 is stacked over the G18 and A19 sugar-phosphate backbone on the partner strand and the other face is exposed to solvent. A minimally perturbed B-DNA helix is observed for the d[T4-C5-(BP)G6-C7-T8].d[A15-G16-C17-G18-A19] segment centered about the adduct site with Watson-Crick alignment for both the (BP)G6.C17 pair and flanking G.C pairs. A widening of the minor groove at the adduct site is detected that accommodates the BP ring whose long axis makes an angle of ≈45° with the average direction of the DNA helix axis. Our study holds future promise for the characterization of other steroisomerically pure adducts of BP diol epoxides with DNA to elucidate the molecular basis of structure-activity relationships associated with the stereoisomer-dependent spectrum of mutational and carcinogenic activities.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle
Additional Information:© 1992 National Academy of Sciences. Communicated by Allan H. Conney, December 4, 1991. D.J.P. acknowledges many helpful discussions with Prof. Dezider Grunberger and Dr. Leo van Houte on the general subject of polycyclic aromatic hydrocarbon diol epoxide adducts with DNA. N.E.G. is grateful to Profs. R. G. Harvey and S. Amin for gifts of (+)-anti-BPDE during the development of the adduct synthesis. Computations were carried out on the Cray supercomputers at the Department of Energy's National Energy Research Supercomputer Center and the National Science Foundation's San Diego Supercomputing Center. This research was supported by Columbia University Start-Up Funds to D.J.P., by National Institutes of Health Grant CA-20851 and Department of Energy Grant DE-FG02- 88ER60405 to N.E.G., by National Institutes of Health Grant DK-38676 to D.L., by National Institutes of Health Grant CA-28038, Department of Energy Grant DE-FG02-90ER60931, National Science Foundation Grant DMB-8416009 to S.B. and by Department of Energy Contract DE-AC05-840R21400 with Martin-Marietta Energy Systems to B.E.H. 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.
Funding AgencyGrant Number
Columbia UniversityUNSPECIFIED
Department of Energy (DOE)DE-FG02-88ER60405
Department of Energy (DOE)DE-FG02-90ER60931
Department of Energy (DOE)DE-AC05-840R21400
Martin-Marietta Energy SystemsUNSPECIFIED
Issue or Number:5
PubMed Central ID:PMC48564
Record Number:CaltechAUTHORS:20141216-153749188
Persistent URL:
Official Citation:Solution conformation of the major adduct between the carcinogen (+)-anti-benzo[a]pyrene diol epoxide and DNA. M Cosman, C de los Santos, R Fiala, B E Hingerty, S B Singh, V Ibanez, L A Margulis, D Live, N E Geacintov, and S Broyde PNAS 1992 89 (5) 1914-1918; doi:10.1073/pnas.89.5.1914
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:52909
Deposited By: Ruth Sustaita
Deposited On:17 Dec 2014 00:00
Last Modified:10 Nov 2021 19:45

Repository Staff Only: item control page