Inherent stereospecificity in the reaction of aflatoxin B(1) 8,9-epoxide with deoxyguanosine and efficiency of DNA catalysis.

Brown KL, Bren U, Stone MP, Guengerich FP
Chem Res Toxicol. 2009 22 (5): 913-7

PMID: 19301826 · PMCID: PMC3141577 · DOI:10.1021/tx900002g

Kinetic analysis of guanine alkylation by aflatoxin B(1) exo-8,9-epoxide, the reactive form of the hepatocarcinogen aflatoxin B(1), shows the reaction to be >2000 times more efficient in DNA than in aqueous solution, that is, with free 2'-deoxyguanosine. Thermodynamic analysis reveals AFB(1) exo-8,9-epoxide 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 predicted by theoretical calculations [ Bren , U. , et al. ( 2007 ) Chem. Res. Toxciol. 20 , 1134 - 1140 ].

MeSH Terms (8)

Aflatoxin B1 Catalysis Chromatography, High Pressure Liquid Deoxyguanosine DNA Stereoisomerism Tandem Mass Spectrometry Thermodynamics

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