| Autor: |
Rao, Shashidhar N., Lybrand, Terry, Michaud, Dennis, Jerina, D.M., Kollman, Peter A. |
| Zdroj: |
Carcinogenesis; 1989, Vol. 10 Issue 1, p27-38, 12p |
| Abstrakt: |
We present molecular mechanics simulations on models of covalent complexes between the diol-epoxides of the carcinogens benzo[]pyrene, benzo[]pyrene and benzo[] phenanthrene and a DNA pentamer d(GCGCG).d(CGCGC). In all the models, the carcinogen diol-epoxides lie in the minor groove with alkylation to the exocyclic amino group of the guanine. The theoretical calculations on the benzo[]pyrene adducts to the pentamer are qualitatively consistent with the experimentally observed relative reactivities between various isomers. The adduct with the (+) isomer, which is the most carcinogenic of the benzo[]pyrene stereoisomer, is calculated to be the energetically most favored. The relative energetic preferences in the adducts of benzo[]pyrene diolepoxides to the pentanucleotide parallel those of benzo[]pyrene. However, there is no obvious explanation for the lack of biological activity in the diol-epoxides of the former carcinogen from the theoretical calculations. In the case of adducts with the diol-epoxides of benzo[]phenanthrene, the energetically most favored structures are isomers with significant biological activity. The distortions in the double helix are more significant in the complexes with the diol-epoxides of this carcinogen compared to those in the complexes with the diol-epoxides of the other two carcinogens. [ABSTRACT FROM PUBLISHER] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
