Synthesis of 1,N2-(1,3-propano)-2'-deoxyguanosine and incorporation into oligodeoxynucleotides: a model for exocyclic acrolein-DNA adducts.
2'-Deoxyguanosine (3) and native DNA both give rise to exocyclic 1,N2-(1,3-propano)-2'-deoxyguanosine adducts 6 and 7 upon treatment with acrolein (1), a known mutagen, in vitro under physiological conditions. The use of synthetic deoxyoligonucleotides containing adduct 6 or 7 could shed light on the mechanism of the mutagenicity of 1 and on the nature of the structural perturbations present in DNA duplexes where they are present. Unfortunately, this is precluded by the instability of 6 and 7 to the conditions of automated DNA synthesis. We have prepared 1,N2-(1,3-propano)-2'-deoxyguanosine (PdG) (8) as a stable model for 6/7. The structure of 8 has been verified by magnetic resonance, ultraviolet spectroscopy, and mass spectrometry. This moiety has been incorporated into oligodeoxynucleotides via solid-state synthesis technology. Negative ion fast atom bombardment (FAB) mass spectrometry of the pentaoligodeoxynucleotide 5'-GT(PdG)CG-3' verified the identity and position of the modified base. The validity of 8 as a model system for the adduct pair 6/7 in structural and biological studies of DNA duplexes is discussed.
Marinelli
E R
ER
Department of Pharmacological Sciences, School of Medicine, State University of New York, Stony Brook 11794-8651.
Johnson
F
F
Iden
C R
CR
Yu
P L
PL
D000171:Acrolein / Q000737:chemistry / Q000378:metabolism; D001483:Base Sequence; D004247:DNA / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D013058:Mass Spectrometry; D008954:Models, Biological; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D013057:Spectrum Analysis / Q000379:methods
D009841:Oligonucleotides; C060934:1,N(2)-propanodeoxyguanosine; D000171:Acrolein; D004247:DNA; D003849:Deoxyguanosine