Synthesis of 1,N2-(1,3-propano)-2'-deoxyguanosine and incorporation into oligodeoxynucleotides: a model for exocyclic acrolein-DNA adducts
- 1 January 1990
- journal article
- research article
- Published by American Chemical Society (ACS) in Chemical Research in Toxicology
- Vol. 3 (1), 49-58
- https://doi.org/10.1021/tx00013a009
Abstract
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.Keywords
This publication has 18 references indexed in Scilit:
- Dissociation of malondialdehyde mutagenicity in Salmonella typhimurium from its ability to induce interstrand DNA cross-linksMutation Research, 1984
- A STUDY OF CHEMICAL CARCINOGENESIS .61. FORMATION OF CYCLIC 1,N2-PROPANODEOXYGUANOSINE ADDUCTS IN DNA UPON REACTION WITH ACROLEIN OR CROTONALDEHYDE1984
- A STUDY OF CHEMICAL CARCINOGENESIS .49. FORMATION OF CYCLIC 1,N-2-ADDUCTS BY REACTION OF DEOXYGUANOSINE WITH "ALPHA-ACETOXY-N-NITROSOPYRROLIDINE, 4-(CARBETHOXYNITROSAMINO)BUTANAL, OR CROTONALDEHYDE1983
- Structure-mutagenicity relationship in α,β-unsaturated carbonylic compounds and their corresponding allylic alcoholsMutation Research, 1982
- Toxicity, interstrand cross-links and DNA fragmentation induced by ‘activated’ cyclophosphamide in yeast: Comparative studies on 4-hydroperoxy-cyclophosphamide, its monofunctional analogon, acrolein, phosphoramide mustard, and nor-nitrogen mustardChemico-Biological Interactions, 1982
- Mutagenic properties of allylic and α,β-unsaturated compounds: Consideration of alkylating mechanismsXenobiotica, 1982
- Air contaminants encountered by firefightersAihaj Journal, 1980
- CYTO-TOXICITY AND DNA CROSS-LINKING ACTIVITY OF 4-SULFIDOCYCLOPHOSPHAMIDES IN MOUSE LEUKEMIA-CELLS INVITRO1980
- Methylation study of ribonucleosides, deoxyribonucleosides, and 2′-O-methylribonucleosides with trimethylsulphonium hydroxide and trimethylsulphonium iodide. Influence of the 2′-hydroxy-groups on the reactivity of the base moieties of ribonucleosidesJournal of the Chemical Society, Perkin Transactions 1, 1980
- Purine Nucleosides. VI. Further Methylation Studies of Naturally Occurring Purine Nucleosides*Biochemistry, 1964