收稿日期: 2016-10-25
网络出版日期: 2018-03-05
基金资助
国家自然科学基金资助项目(21077070);国家自然科学基金资助项目(21377080);上海市教委科研创新基金重点资助项目(11ZZ90);上海市重点学科建设资助项目(S30109)
Reaction of 1-chloro-3-buten-2-one with N-acetylcysteine
Received date: 2016-10-25
Online published: 2018-03-05
1-氯-3-丁烯-2-酮(1-chloro-3-buten-2-one, CBO)是致癌性环境污染物1,3-丁二烯的一种体外代谢产物, 具有细胞毒性和遗传毒性, 易形成DNA加成产物以及谷胱甘肽偶联产物. 预计CBO-谷胱甘肽偶联产物在肾脏被代谢为CBO-N-乙酰半胱氨酸(N-acetylcysteine, NAC)偶联产物, 最终随尿排出体外. 因此, CBO-NAC偶联产物能够作为CBO生物标志物. 然而, CBO与NAC的反应尚未见报道. 研究了CBO与NAC在体外生理条件下(pH=7.4, 37 ℃)的反应, 观察到两种产物. 通过一维和二维核磁共振光谱(nuclear magnetic resonance spectroscopy, NMR)确定两种产物的结构分别是1-氯-4-(N-乙酰-S-半胱氨酸基)-2-丁酮和1,4-双(N-乙酰-S-半胱氨酸基)-2-丁酮, 后者是一种新化合物. 这些产物的识别为后续研究打好了基础.
刘柏良, 张新宇 . 1-氯-3-丁烯-2-酮与N-乙酰半胱氨酸的反应[J]. 上海大学学报(自然科学版), 2018 , 24(1) : 74 -82 . DOI: 10.12066/j.issn.1007-2861.1846
1-Chloro-3-buten-2-one (CBO) is an in vitro metabolite of 1,3-butadiene, a carcinogenic pollutant.CBO is cytotoxic and genotoxic, and can readily form DNA adducts and glutathione (GSH) conjugates. CBO-GSH conjugates are expected to be biotransformed into CBO-N-acetylcysteine (NAC) ones in the kidney, which are excreted in the urine. Thus, CBO-NAC conjugates can be used as biomarkers. However, the reaction of CBO with NAC has not been investigated yet. In the present study, this reaction under in vitro physiological conditions (pH=7.4, 37 ℃) was investigated and two products, which were structurally characterized by 1D/2D nuclear magnetic resonance (NMR) spectroscopy as 1-chloro-4-(N-acetyl-S-cysteinyl)-2-butanone and 1,4-bis(N-acetyl-S-cysteinyl)-2-butanone, were observed. The latter is a novel compound. Identification of the two CBO-NAC conjugates will help future investigation on the in vivo formation of CBO.
Key words： 1-chloro-3-buten-2-one; N-acetylcysteine; 1; 3-butadiene; metabolite; biomarker
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