Structural identification of the pyrimidine derivatives formed from N-(deoxyguanosin-8-yl)-2-aminofluorene in aqueous solution at alkaline pH.
The major aminofluorene-DNA derivative formed from the carcinogen N-acetyl-2-aminofluorene in vivo in rat liver is N-(deoxyguanosin-8-yl)-2-aminofluorene. This nucleoside is hydrolyzed in aqueous solution at alkaline pH through the 7-8 guanine bond to form two pyrimidine derivatives which were separated by Sephadex LH-20 column chromatography and thin-layer chromatography on silica. From chemical, u.v., i.r., n.m.r. and mass spectral analysis the pyrimidine derivatives have been identified as 1-[6-(2,5-diamino-4-oxopyrimidinyl-N6-deoxyriboside)]-3-(2-fluorenyl)ureas, which probably are stereoisomers. Similar products were isolated from enzymatic hydrolysates of DNA reacted with N-hydroxy-2-aminofluorene under mildly acidic conditions (pH 5) and subsequent treatment with 0.1 N NaOH. Kinetic studies of the hydrolysis reaction showed that it occurs already at a measurable rate at pH 9.5 and 37 degrees C. The reaction is catalyzed by Mg2+ and Mn2+ ions and by alkaline phosphatase from E. coli.
D015073:2-Acetylaminofluorene / Q000031:analogs & derivatives* / Q000032:analysis; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis; D005449:Fluorenes; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D011743:Pyrimidines / Q000032:analysis*
D005449:Fluorenes; D011743:Pyrimidines; C031838:N-(deoxyguanosin-8-yl)-2-aminofluorene; C018776:N-(deoxyguanosin-8-yl)acetylaminofluorene; D004247:DNA; D015073:2-Acetylaminofluorene; D003849:Deoxyguanosine