Synthesis of the PhIP adduct of 2′-deoxyguanosine and its incorporation into oligomeric DNA

被引：10

作者：

Bonala, Radha ^{[1
]}

Torres, M. Cecilia ^{[1
]}

Iden, Charles R. ^{[1
]}

Johnson, Francis ^{[1
]}

机构：

[1] SUNY Stony Brook, Dept Pharmacol Sci, Stony Brook, NY 11794 USA

来源：

CHEMICAL RESEARCH IN TOXICOLOGY | 2006年 / 19卷 / 06期

关键词：

D O I：

10.1021/tx0600191

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The 2'-deoxyguanosine adduct of the dietary mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) has been synthesized and incorporated into DNA using solid state synthesis technology. The key step to obtaining the C8-dG adduct is a palladium (Xantphos-chelated)-catalyzed-N-arylation (Buchwald-Hartwig reaction) of PhIP by a suitably protected 8-bromo-2'-deoxyguanosine derivative. The reaction proceeded in good yield without complicating side products, and the adduct was converted to the required 5'-O-DMT-3'-O-phosphoramidite by standard methods. This modified deoxynucleoside was used to synthesize three oligodeoxynucleotides in which the C8-PhIP-dG adduct was incorporated at a single site. The oligomers were purified by reverse phase HPLC and characterized by mass spectrometry.

引用

页码：734 / 738

页数：5

共 15 条

[1] ANALYSIS OF DNA-ADDUCTS OF 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE IN RAT AND HUMAN TISSUES BY ALKALINE-HYDROLYSIS AND GAS-CHROMATOGRAPHY ELECTRON-CAPTURE MASS-SPECTROMETRY - VALIDATION BY COMPARISON WITH P-32 POSTLABELING [J].

FRIESEN, MD ;

KADERLIK, K ;

LIN, DX ;

GARREN, L ;

BARTSCH, H ;

LANG, NP ;

KADLUBAR, FF .

CHEMICAL RESEARCH IN TOXICOLOGY, 1994, 7 (06) :733-739

[2]

Garner RC, 1998, MUTAT RES-FUND MOL M, V402, P67

[3] Synthesis of the minor acrolein adducts of 2′-deoxyguano sine and their generation in oligomeric DNA [J].

Huang, YH ;

Torres, MC ;

Iden, CR ;

Johnson, F .

BIOORGANIC CHEMISTRY, 2003, 31 (02) :136-148

[4] A NEW COLON AND MAMMARY CARCINOGEN IN COOKED FOOD, 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE (PHIP) [J].

ITO, N ;

HASEGAWA, R ;

SANO, M ;

TAMANO, S ;

ESUMI, H ;

TAKAYAMA, S ;

SUGIMURA, T .

CARCINOGENESIS, 1991, 12 (08) :1503-1506

[5] Efficient synthesis of the benzo[a]pyrene metabolic adducts of 2′-deoxyguanosine and 2′-deoxyadenosine and their direct incorporation into DNA [J].

Johnson, F ;

Bonala, R ;

Tawde, D ;

Torres, MC ;

Iden, CR .

CHEMICAL RESEARCH IN TOXICOLOGY, 2002, 15 (12) :1489-1494

[6] IDENTIFICATION OF N-(DEOXYGUANOSIN-8-YL)-2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE AS THE MAJOR ADDUCT FORMED BY THE FOOD-BORNE CARCINOGEN, 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE, WITH DNA [J].

LIN, DX ;

KADERLIK, KR ;

TURESKY, RJ ;

MILLER, DW ;

LAY, JO ;

KADLUBAR, FF .

CHEMICAL RESEARCH IN TOXICOLOGY, 1992, 5 (05) :691-697

[7] CARCINOGENIC TRYPTOPHAN PYROLYSIS PRODUCTS IN CIGARETTE-SMOKE CONDENSATE AND CIGARETTE SMOKE-POLLUTED INDOOR AIR [J].

MANABE, S ;

WADA, O .

ENVIRONMENTAL POLLUTION, 1990, 64 (02) :121-132

[8] CARCINOGENIC TRYPTOPHAN PYROLYSIS PRODUCTS IN AIRBORNE PARTICLES AND RAIN WATER [J].

MANABE, S ;

UCHINO, E ;

WADA, O .

MUTATION RESEARCH, 1989, 226 (04) :215-221

[9] DETECTION OF A CARCINOGEN, 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE (PHIP), IN CIGARETTE-SMOKE CONDENSATE [J].

MANABE, S ;

TOHYAMA, K ;

WADA, O ;

ARAMAKI, T .

CARCINOGENESIS, 1991, 12 (10) :1945-1947

[10] 32POSTLABELLING ANALYSIS OF URINARY MUTAGENS FROM SMOKERS OF BLACK TOBACCO IMPLICATES 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE (PHIP) AS A MAJOR DNA-DAMAGING AGENT [J].

PELUSO, M ;

CASTEGNARO, M ;

MALAVEILLE, C ;

FRIESEN, M ;

GARREN, L ;

HAUTEFEUILLE, A ;

VINEIS, P ;

KADLUBAR, F ;

BARTSCH, H .

CARCINOGENESIS, 1991, 12 (04) :713-717

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