Synthesis of 8-(hydroxymethyl)-3,N4-etheno-2'-deoxycytidine, a potential carcinogenic glycidaldehyde adduct, and its site-specific incorporation into DNA oligonucleotides

被引：9

作者：

Chenna, A ^{[1
]}

Perry, A ^{[1
]}

Singer, B ^{[1
]}

机构：

[1] Univ Calif Berkeley, Lawrence Berkeley Lab, Donner Lab, Div Life Sci, Berkeley, CA 94720 USA

来源：

CHEMICAL RESEARCH IN TOXICOLOGY | 2000年 / 13卷 / 03期

关键词：

D O I：

10.1021/tx990181m

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The previously unreported glycidaldehyde adduct, 8-(hydroxymethyl)-3,N-4-etheno-2'-deoxycytidine (8-HM-epsilon dC), has been synthesized for the first time by reaction of 2'-deoxycytidine with bromoacetaldehyde at pH 4.5, followed by reduction with sodium borohydride. The adduct was characterized by UV, MS, and NMR. The compound was stable to neutral and acidic conditions but not in alkaline solution. The corresponding phosphoramidite was synthesized in good yield from the intermediate, 3,N-4-ethenocarbaldehyde-2'-deoxycytidine using the standard methodology and site-specifically incorporated in both 15- and 25-mer oligonucleotides, for studies on biochemical and biophysical properties. The resulting oligonucleotides were purified using HPLC, and the base composition was verified by HPLC after enzymatic digestion.

引用

页码：208 / 213

页数：6

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