Pyrimido[1,2-alpha]purin-10(3H)-one: a reactive electrophile in the genome.
Pyrimido[1,2-alpha]purin-10(3H)-one: a reactive electrophile in the genome.
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Pyrimido[1,2-α]purin-10(3H)-one：基因组中的反应性亲电子试剂。
DOI：
10.1021/tx000135i
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发表时间：
2000
影响因子：
4.1
通讯作者：
Marnett,LJ
中科院分区：
文献类型：
--
作者：
Schnetz-Boutaud,N;Daniels,JS;Hashim,MF;Scholl,P;Burrus,T;Marnett,LJ
Malondialdehyde and base propenal react with deoxyguanosine residues in DNA to form an exocyclic adduct, pyrimido[1,2-α]purin-10(3H)-one (1), that has been detected at high levels in genomic DNA of healthy humans. Previous studies have shown that tris(hydroxymethyl)aminomethane adds to1at elevated pH, forming an enaminoimine (2), but it is uncertain whether1reacts directly or hydrolyzes under basic conditions toN2-(3-oxo-1-propenyl)deoxyguanosine (3) prior to amine addition. We report that1reacts at neutral pH with hydroxylamines to form oximes. The rate of reaction of1with hydroxylamines at pH 7 is at least 150 times faster than the rate of hydrolysis of1to3. Thus,1is directly reactive to nucleophiles. These observations indicate that1is an electrophile in the human genome that may react with cellular nucleophiles to form novel cross-linked adducts.
