Synthesis and characterization of nucleosides and oligonucleotides bearing adducts of butadiene epoxides on adenine n(6) and guanine n(2).
Butadiene is a major industrial chemical whose genotoxic effects are attributed to the reaction of its oxidized metabolites, butadiene monoepoxide (BDO) and butadiene diepoxide (BDO2), with DNA. Nucleosides and oligonucleotides containing regio- and stereochemically specific adducts of BDO and the BDO2-related compound, butene 3,4-diol 1,2-epoxide (BDE), on guanine [(2R)- and (2S)-N(2)-(1-hydroxy-3-buten-2-yl) and (2R,3R)- and (2S,3S)-N(2)-(2,3,4-trihydroxybut-1-yl), respectively] and on adenine [(2R)- and (2S)-N(6)-(1-hydroxy-3-buten-2-yl) and (2R,3R)- and (2S,3S)-N(6)-(2,3,4-trihydroxybut-1-yl), respectively] have been prepared by nonbiomimetic routes. For guanine adducts, 2-fluoro-O(6)-(trimethylsilylethyl)-2'-deoxyinosine was treated with (2R)- and (2S)-2-amino-3-buten-1-ol to give the BDO adducts and with (2R,3R)- and (2S,3S)-1-amino-2,3,4-butanetriol to produce the BDE adducts; the adducted oligonucleotides were prepared from 11-mer oligonucleotides containing the halopurine. Adenine adducts were prepared in a similar fashion using 6-chloropurine 2'-deoxyriboside as the reactive purine component.
Nechev
L V
LV
Chemistry Department and Center in Molecular Toxicology, Vanderbilt University, Nashville, TN 37235, USA.
Zhang
M
M
Tsarouhtsis
D
D
Tamura
P J
PJ
Wilkinson
A S
AS
Harris
C M
CM
Harris
T M
TM
D000225:Adenine / Q000737:chemistry*; D001483:Base Sequence; D002942:Circular Dichroism; D004852:Epoxy Compounds / Q000737:chemistry*; D006147:Guanine / Q000737:chemistry*; D013058:Mass Spectrometry; D019906:Nuclear Magnetic Resonance, Biomolecular; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry
D004852:Epoxy Compounds; D009705:Nucleosides; D009841:Oligonucleotides; C024370:3,4-epoxy-1-butene; D006147:Guanine; D000225:Adenine