Effect of Absolute Configuration on the Optical and NMR Properties of Oligonucleotides Containing Benzo[a]Pyrene Adducts at N 6 of Deoxyadenosine |
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Authors: | Jane M Sayer Jamshed H Shah Chengyi Liang Guojian Xie Heiko Kroth Haruhiko Yagi |
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Affiliation: | Laboratory of Bioorganic Chemistry , National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Bethesda, MD, 20892-0820 |
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Abstract: | For oligonucleotide duplexes derived from trans opening of benzoa]pyrene diol epoxides (BaP DEs) by the exocyclic N6-amino group of deoxyadenosine (dA), the hydrocarbon is intercalated toward the 5′-end of the modified strand when the configuration at the site of attachment of the base to the hydrocarbon (C-10) is R, and toward the 3′-end when this configuration is S. In oligonucleotide 11-mer duplexes modified by BaP DE-1 (benzylic 7-OH and epoxide oxygen cis) and DE-2 (7-OH and epoxide oxygen trans), as well as 7,8,9,10-tetrahydro BaP 9,10-epoxide, 10R adducts had consistently higher (5–9d°C) Tm values than the corresponding 10S adducts. Dodecamer duplexes from the HPRT gene with trans opened 10S (but not those with 10R) BaP DE-2 adducts at either of two adjacent dA residues exhibited blue shifts at ~350 nm at temperatures well below the Tm. We propose that these blue shifts result from a conformation in which the hydrocarbon is not stacked with the DNA bases. |
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Keywords: | benzo[a]pyrene diol epoxides deoxyadenosine adducts oligonucleotides thermal denaturation ultraviolet spectra NMR |
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