Inherent Stereospecificity in the Reaction of Aflatoxin B1 8,9-Epoxide with Deoxyguanosine and Efficiency of DNA Catalysis

被引：30

作者：

Brown, Kyle L. ^{[1
]}

Bren, Urban ^{[3
]}

Stone, Michael P. ^{[1
,2
]}

Guengerich, F. Peter ^{[1
,2
]}

机构：

[1] Vanderbilt Univ, Ctr Mol Toxicol, Nashville, TN 37232 USA

[2] Vanderbilt Univ, Dept Chem & Biochem, Nashville, TN 37232 USA

[3] Natl Inst Chem, SI-1001 Ljubljana, Slovenia

来源：

CHEMICAL RESEARCH IN TOXICOLOGY | 2009年 / 22卷 / 05期

关键词：

EPOXIDES; ADDUCTS; BINDING; EXO-8,9-EPOXIDE; INTERCALATION; SPECTROSCOPY; SUPPRESSION; HYDROLYSIS; WET;

D O I：

10.1021/tx900002g

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 deoxyguarrosine (ratio >20:1 determined by LC-MS and NMR measurements), as predicted by theoretical calculations [Bren, U., et at. (2007) Chem. Res. Toxciol. 20, 1134-1140].

引用

页码：913 / 917

页数：5

共 25 条

[11] Kinetics and mechanism of hydrolysis of aflatoxin B-1 exo-8,9-epoxide and rearrangement of the dihydrodiol [J].

Johnson, WW ;

Harris, TM ;

Guengerich, FP .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1996, 118 (35) :8213-8220

[12]

MARIEN K, 1987, J BIOL CHEM, V262, P7455

[13] SELECTIVE TRAPPING OF N-ACETYL-N-(4-BIPHENYLYL)NITRENIUM AND N-ACETYL-N-(2-FLUORENYL)NITRENIUM IONS BY 2'-DEOXYGUANOSINE IN AQUEOUS-SOLUTION [J].

NOVAK, M ;

KENNEDY, SA .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1995, 117 (01) :574-575

[14] WET, A T-1-INSENSITIVE AND B-1-INSENSITIVE WATER-SUPPRESSION METHOD FOR IN-VIVO LOCALIZED H-1-NMR SPECTROSCOPY [J].

OGG, RJ ;

KINGSLEY, PB ;

TAYLOR, JS .

JOURNAL OF MAGNETIC RESONANCE SERIES B, 1994, 104 (01) :1-10

[15] ALTERATION OF THE AFLATOXIN CYCLOPENTENONE RING TO A DELTA-LACTONE REDUCES INTERCALATION WITH DNA AND DECREASES FORMATION OF GUANINE-N7 ADDUCTS BY AFLATOXIN EPOXIDES [J].

RANEY, KD ;

GOPALAKRISHNAN, S ;

BYRD, S ;

STONE, MP ;

HARRIS, TM .

CHEMICAL RESEARCH IN TOXICOLOGY, 1990, 3 (03) :254-261

[16] THE ENDO-8,9-EPOXIDE OF AFLATOXIN-B1 - A NEW METABOLITE [J].

RANEY, KD ;

COLES, B ;

GUENGERICH, FP ;

HARRIS, TM .

CHEMICAL RESEARCH IN TOXICOLOGY, 1992, 5 (03) :333-335

[17] GLUTATHIONE CONJUGATION OF AFLATOXIN-B1 EXO-EPOXIDES AND ENDO-EPOXIDES BY RAT AND HUMAN GLUTATHIONE S-TRANSFERASES [J].

RANEY, KD ;

MEYER, DJ ;

KETTERER, B ;

HARRIS, TM ;

GUENGERICH, FP .

CHEMICAL RESEARCH IN TOXICOLOGY, 1992, 5 (04) :470-478

[18] DNA CONFORMATION MEDIATES AFLATOXIN B1-DNA BINDING AND THE FORMATION OF GUANINE N7 ADDUCTS BY AFLATOXIN-B1 8,9-EXO-EPOXIDE [J].

RANEY, VM ;

HARRIS, TM ;

STONE, MP .

CHEMICAL RESEARCH IN TOXICOLOGY, 1993, 6 (01) :64-68

[19]

Searle C.E., 1984, CHEM CARCINOGENS, VI

[20]

SEARLE CE, 1984, CHEM CARCINOGENS, V2

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