Kinetic analysis of guanine alkylation by aflatoxin B1 exo-8,9-epoxide, the reactive form of the hepatocarcinogen AFB1, shows the reaction to be > 2000 times more efficient in DNA than in aqueous solution, that is, with free 2'-deoxyguanosine. Thermodynamic analysis reveals AFB1 intercalation as the predominant source of the observed DNA catalytic effect. However, the known exo > endo epoxide stereospecificity of the DNA alkylation is observed even with free deoxyguanosine (ratio > 20:1 determined by LC-MS and NMR measurements), as beforehand predicted by our theoretical calculations.
COBISS.SI-ID: 4132890
Deoxyinosine and deoxyxanthosine (dX) are both formed in DNA at appreciable levels in vivo by deamination of deoxyadenosine and deoxyguanosine and can miscode. The replicative bacteriophage T7 DNA polymerase/exonuclease and the translesion DNA polymerase Sulfolobus solfataricus pol IV were used as models to discern the mechanisms of miscoding by DNA polymerases. Linear activity models show the effects of oxygen (dX) and the halogens at C2 on both DNA polymerases as mainly due to a combination of both steric and electrostatic factors, producing a clash with the paired cytosine O2 atom.
COBISS.SI-ID: 4199450