The structure of oligodeoxynucleotides modified by the environmental carcinogens benzo(a)pyrene diol epoxide and the carcinogens N-2-(acetylamino)fluorene and N2-(amino)fluorene will be determined by the use of two-dimensional NMR spectroscopy. The distances obtained from NOESY data will be used as restraints in molecular mechanics and molecular dynamics calculations. The three dimensional structures of adducts bound to different sequences will be determined to elucidate the effect of sequence on the structure and dynamics of the adducts. Carcinogen-modified oligodeoxynucleotides will be synthesized containing either codon 12 or codon 61 sequences of the mouse and human c-Ha-ras 1 protooncogenes and the structures determined with covalently attached carcinogens at the guanines which are mutated in activating the oncogenes.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM053826-13
Application #
2023216
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1983-08-01
Project End
1999-11-30
Budget Start
1996-12-01
Budget End
1997-11-30
Support Year
13
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Rochester
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627
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