DNA alkylation is a well-established consequence of the introduction of mutagens and carcinogens into the cellular environment. Recent studies have shown that alkylation of the sugar-phosphate backbone results upon exposure to such potent carcinogens as ethyl nitrosourea. Although it is not yet established what role the formation of phosphotriesters takes in inducing DNA misfunction, it has been postulated that structural perturbations are important. The stereochemistry of the alkyl- phosphate moiety appears to play a significant role in the effects of backbone alkylation, and changes in phosphate hydration may also be important. Investigations of structural perturbations in the DNA octamer, (d-(GGAATTCC))2 induced following site- specific and stereochemical-specific phosphate alkylation will be performed using NMR spectroscopy. Experiments will include temperature dependent proton and phosphorus one-dimensional experiments and two-dimensional experiments coupled with theoretical analyses.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29CA046713-03
Application #
3458715
Study Section
Biophysics and Biophysical Chemistry A Study Section (BBCA)
Project Start
1987-07-01
Project End
1990-08-15
Budget Start
1989-07-01
Budget End
1990-08-15
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Hunter College
Department
Type
Schools of Arts and Sciences
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10065