A comprehensive study at the molecular level of the initiation step in chemical carcinogenesis is proposed. The conformation and function of carcinogen-modified DNA will be examined in DNA oligomers of specific length and sequence and bearing specific lesions. The principal tools in the investigation are 1H, 13C and 31P NMR spectroscopies supplemented also by X-ray diffraction studies. The effects of both alkylating and bulky carcinogens in DNA structure and function will be studied. A representative group of DNA lesions will be examined in the sense that all the major sites of reaction in DNa will be represented. The proposed investigation is made feasible by a synthesis program which will provide the quantities of modified DNA oligomers needed particularly for the 13C NMR, two-dimensional 1H NMR, and X-ray diffraction studies. It is anticipated that most of the investigations will be done on modified DNA hexamers of d(TpApCpGpTpAp) although various sequences will be synthesized as the need arises.
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| Sharma, M; Box, H C (1985) Synthesis, modification with N-acetoxy-2-acetylaminofluorene and physicochemical studies of DNA model compound d(TACGTA). Chem Biol Interact 56:73-88 |
