Synthesis of the minor acrolein adducts of 2(')-deoxyguanosine and their generation in oligomeric DNA.
Acrolein, a known mutagen, undergoes reaction in vitro under physiological conditions with both 2(')-deoxyguanosine and native DNA to give rise to exocyclic adducts of the 5,6,7,8-tetrahydropyrimido[1,2-a]purine-10(3H)-one class having an hydroxy group at either the 6 or the 8 position. Previously we have shown that the 8-hydroxy derivative in a bacterial system has very low mutagenicity probably because in double-stranded DNA this residue exists in the open-chain aldehydic form [N(2)-(3-oxopropyl)-2(')-deoxyguanosine] (3). To continue our investigation in this area, we needed ample supplies of the 6-hydroxy isomers. This current paper describes high-yield simple methods for the synthesis in bulk of the 6-hydroxy adduct 1 and its incorporation into DNA oligomers. The basic methods for the synthesis of the adduct 1, involve 1-substitution of dG derivatives with a 3-butenyl group, dihydroxylation of the olefin with osmium tetroxide and N-methylmorpholine N-oxide, then diol cleavage with periodate ion after incorporation of the 1-(3,4-diacetoxybutyl)-2(')-deoxyguanosine into oligomeric DNA.
Huang
Yanhe
Y
Department of Pharmacological Sciences, State University of New York at Stony Brook, Stony Brook, NY 11794, USA.
Cecilia Torres
M
M
Iden
Charles R
CR
Johnson
Francis
F
D000171:Acrolein / Q000138:chemical synthesis* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D018736:DNA Adducts / Q000737:chemistry*; D003849:Deoxyguanosine / Q000138:chemical synthesis* / Q000737:chemistry; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry
D018736:DNA Adducts; D009841:Oligonucleotides; D000171:Acrolein; D003849:Deoxyguanosine