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.
| Broido, M S; Mezei, M (1990) Computational analysis of the effects of site-specific phosphate alkylation in the DNA oligomer (d-[GGAATTCC])2. Biopolymers 29:597-607 |
