氨基酸和脱氧核化物及其寡合体之间的甲诱导交叉链的结构性表征
1Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Journal of the American Chemical Society
|February 25, 2010
概括
甲暴露会导致DNA-蛋白质交叉链接 (DPC). 这项研究描述了氨基酸和DNA基之间的甲诱导的交叉链接,揭示了甲桥和三环,有助于生物标记物识别.
科学领域:
- 化学生物学 化学生物学
- 基因毒理学 基因毒理学
- 分子毒理学 分子毒理学
背景情况:
- 甲是一种致基因毒剂,导致DNA-蛋白质交叉链接 (DPC).
- 甲诱导的DPC的特定结构在很大程度上仍未被阐明.
- 已知有8种氨基酸与甲形成稳定的添加物.
研究的目的:
- 描述氨基酸和DNA基之间的甲诱导的交叉链的结构.
- 确定哪些氨基酸和DNA基与甲形成稳定的交叉链接.
- 为了解体内DPC形成和开发甲暴露生物标志物提供结构性见解.
主要方法:
- 甲与特定氨基酸 (Lys,Cys,His,Trp) 和DNA基 (dG,dA,dC) 的反应.
- 使用核磁共振 (NMR) 和质谱学进行结构性表征.
- 分析由单核化物,三核化物和8分子形成的交叉链接.
主要成果:
- 氨酸和dG显示了交叉链接产品的最高产量,其次是Cys和dG.
- 交叉链主要涉及氨基酸和核酸之间的甲甲衍生的甲桥.
- 氨酸与dG形成了附加产物,其中含有1,N(2) 融合的氨酸环;这些产物是不稳定的.
- 使用NMR,质谱和碎片化模式确认了结构.
结论:
- 已经阐明了甲诱导的DNA-蛋白质交叉链的详细结构.
- 已识别的结构包括甲桥和三环.
- 这些发现将有助于在体内研究DPC,并开发甲暴露的生物标志物.
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