Synthesis of the PhIP adduct of 2'-deoxyguanosine and its incorporation into oligomeric DNA.
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.
Bonala
Radha
R
Department of Pharmacological Sciences, Stony Brook University, New York 11794-3400, USA.
Torres
M Cecilia
MC
Iden
Charles R
CR
Johnson
Francis
F
D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000138:chemical synthesis* / Q000737:chemistry; D003849:Deoxyguanosine / Q000737:chemistry*; D005502:Food; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D009153:Mutagens / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization
D007093:Imidazoles; D009153:Mutagens; D004247:DNA; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D003849:Deoxyguanosine