Synthesis of Nucleosides and Oligonucleotides Containing Adducts of Acrolein and Vinyl Chloride
- 21 April 2000
- journal article
- research article
- Published by American Chemical Society (ACS) in Chemical Research in Toxicology
- Vol. 13 (5) , 421-429
- https://doi.org/10.1021/tx990167+
Abstract
Vinyl chloride and acrolein are important industrial chemicals. Both form DNA adducts, vinyl chloride after enzymatic oxidation to chlorooxirane and acrolein by direct reaction. Reaction at the N2 position of guanine is a major pathway. The resulting 2-oxoethyl and 3-oxopropyl adducts cyclize spontaneously to hydroxyethano and hydroxypropano derivatives, respectively. The two cyclic adducts have been detected in DNA exposed to these mutagens. A new method has been developed for the synthesis of deoxyguanosine adducts of chlorooxirane and acrolein, as well as oligonucleotides containing these adducts. Reaction of O6-[(trimethylsilyl)ethyl]-2-fluoro-2‘-deoxyinosine with the appropriate aminodiol followed by oxidative cleavage of the diol with NaIO4 gave the adducts in excellent yields. Reaction of oligonucleotides containing the halonucleoside with the aminodiols followed by NaIO4 efficiently created the nucleosides in the oligonucleotides. Deoxyadenosine adducts were created similarly using 6-chloropurine 9-(2‘-deoxyriboside).Keywords
This publication has 15 references indexed in Scilit:
- Postsynthetic Generation of a Major Acrolein Adduct of 2‘-Deoxyguanosine in Oligomeric DNA†Journal of Medicinal Chemistry, 1999
- Misincorporation of Nucleotides opposite Five-Membered Exocyclic Ring Guanine Derivatives by Escherichia coli Polymerases in Vitro and in Vivo: 1,N2-Ethenoguanine, 5,6,7,9-Tetrahydro-9-oxoimidazo[1,2-a]purine, and 5,6,7,9-Tetrahydro-7-hydroxy-9-oxoimidazo[1,2-a]purineBiochemistry, 1998
- Sequence context is an important determinant in the mutagenic potential of 1,N6-ethenodeoxyadenosine (epsilonA): formation of epsilonA basepairs and elongation in defined templatesCarcinogenesis: Integrative Cancer Research, 1997
- Misincorporation of dNTPs Opposite 1,N2-Ethenoguanine and 5,6,7,9-Tetrahydro-7-hydroxy-9-oxoimidazo[1,2-a]purine in Oligonucleotides by Escherichia coli Polymerases I exo- and II exo-, T7 Polymerase exo-, Human Immunodeficiency Virus-1 Reverse Transcriptase, and Rat Polymerase βBiochemistry, 1997
- Mutagenicity of vinyl chloride and its reactive metabolites, chloroethylene oxide and chloroacetaldehyde, in a metabolically competent human B-lymphoblastoid lineCarcinogenesis: Integrative Cancer Research, 1997
- Synthesis of Oligonucleotides Containing Interchain Cross-Links of Bifunctional PyrrolesJournal of the American Chemical Society, 1995
- Proton NMR of an oligodeoxynucleotide containing a propanodeoxyguanosine adduct positioned in a (CG)3 frameshift hotspot of Salmonella typhimurium hisD3052: Hoogsteen base-pairing at pH 5.8Chemical Research in Toxicology, 1993
- Roles of the vinyl chloride oxidation products 2-chlorooxirane and 2-chloroacetaldehyde in the in vitro formation of etheno adducts of nucleic acid basesChemical Research in Toxicology, 1992
- Formation of etheno adducts of adenosine and cytidine from 1-halooxiranes. Evidence for a mechanism involving initial reaction with the endocyclic nitrogen atomsJournal of the American Chemical Society, 1992
- Evidence for acrolein-modified DNA in peripheral blood leukocytes of cancer patients treated with cyclophosphamideMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 1991