Chemical synthesis of cross-link lesions found in nitrous acid treated DNA: a general method for the preparation of N2-substituted 2'-deoxyguanosines.
Treatment of DNA with nitrous acid results in the formation of DNA-DNA cross-links. Two cross-link lesions have previously been isolated and their structures assigned based on spectroscopic data. The major lesion has been proposed to consist of two deoxyguanosine (dG) nucleosides sharing a common N2 atom (1), while the structure of the minor lesion has been proposed to consist of a common nitrogen atom linking C2 of a dG nucleoside to C6 of deoxyadenosine (2). The chemical synthesis of 1 and 2, utilizing a palladium-catalyzed coupling, is described herein. It is demonstrated that the spectroscopic properties of synthetic 1 are identical to that of lesion 1 obtained from nitrous acid cross-linked DNA, thus providing a proof of its structure. Comparison of the limited spectroscopic data available for lesion 2 originating from nitrous acid cross-linked DNA to synthetic 2 supports its structural assignment. The synthetic approach used for synthesis of 1 and 2 is shown to be a general method for the preparation of a variety of N2-substituted dG nucleosides in good yields.
Harwood
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EA
Department of Chemistry, University of Washington, Box 351700, Seattle, Washington 98195, USA.
Hopkins
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PB
Sigurdsson
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D002384:Catalysis; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004247:DNA / Q000737:chemistry* / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D009608:Nitrous Acid / Q000737:chemistry*; D010165:Palladium; D013056:Spectrophotometry, Ultraviolet
D003432:Cross-Linking Reagents; D007202:Indicators and Reagents; D010165:Palladium; D004247:DNA; D003849:Deoxyguanosine; D009608:Nitrous Acid