Synthesis of cis Adducts of Cyclopenta[cd]Pyrene with Deoxyguanosine and Deoxyadenosine |
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Authors: | R Sangaiah C M Prusiewicz J J Hayward A Gold L M Ball |
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Affiliation: | Department of Environmental Sciences and Engineering , University of North Carolina at Chapel Hill , Chapel Hill, North Carolina, 27599-7400, USA |
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Abstract: | Recent analysis of DNA adducts of cyclopentacd]pyrene (CPP) formed in vitro by reaction of CPP-3, 4-oxide, with calf thymus DNA, suggested ring opening of the enantiomeric 3,4-epoxide predominantly by cis addition. We describe herein the chemical synthesis of DNA adducts resulting from benzylic cis ring opening of CPP-3,4-oxide by the exocyclic amino group of 2′-deoxyguanosine (dG) and 2′-deoxyadenosine (dA). The methodology involves synthesis of cis-3,4-dihydro-3-amino-4-hydroxycyclopentacd]pyrene followed by its coupling with appropriately protected halo-purinedeoxyribose intermediates. The diastereomeric mixture of products resulted in the coupling reaction was separated by HPLC and characterized by 1H NMR and MS analysis. Co-chromatography of the synthetic standards with in vitro adducts confirmed the identity and the stereochemical preference of the CPP-DNA adducts. |
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Keywords: | CPP DNA adducts cis addition |
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