Interchain cross-linking of DNA mediated by the principal adduct of acrolein

被引:61
|
作者
Kozekov, ID
Nechev, LV
Sanchez, A
Harris, CM
Lloyd, RS
Harris, TM
机构
[1] Vanderbilt Univ, Dept Chem, Nashville, TN 37235 USA
[2] Vanderbilt Univ, Ctr Mol Toxicol, Nashville, TN 37235 USA
[3] Univ Texas, Med Branch, Sealy Ctr Mol Sci, Galveston, TX 77555 USA
关键词
D O I
10.1021/tx010127h
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
A DNA duplex containing the primary acrolein adduct, 3-(2-deoxy-beta -D-erythro-pentofuranosyl)-5,6,7,8-tetrahydro-8-hydroxypyrimido[1,2-a]purin-10(3H)-one (2), of deoxyguanosine in a 5'-CpG sequence context spontaneously but reversibly formed an interchain cross-link with the exocyclic amino group of deoxyguanosine in the opposing chain. The linkage was sufficiently stable that the cross-linked duplex could be isolated by HPLC and characterized by MALDI-TOF mass spectrometry. Enzymatic degradation gave his-nucleoside 6, which was independently prepared by direct reaction of 2 with dGuo.
引用
收藏
页码:1482 / 1485
页数:4
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