Chen Shu-Hui, Li Chun-Wei
Department of Chemistry, National Cheng Kung University, Tainan, Taiwan.
Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan.
Front Chem. 2019 Aug 21;7:571. doi: 10.3389/fchem.2019.00571. eCollection 2019.
The catechol quinone (CQ) motif is present in many biologically relevant molecules throughout endogenous metabolic products, foods, drugs, and environmental pollutants. The CQ derivatives may undergo Michael addition, and has been shown to yield covalent bonds with nucleophilic sites of cysteine, lysine, or histidine residue of proteins. The CQ-adducted proteins may exhibit cytotoxicity or biological functions different from their un-adducted forms. Identification, characterization, and quantification of relevant protein targets are essential but challenging goals. Mass spectrometry (MS) is well-suited for the analysis of proteins and protein modifications. Technical development of bottom-up proteomics has greatly advanced the field of biomolecular MS, including protein adductomics. This mini-review focuses on the use of biomolecular MS in (1) structural and functional characterization of CQ adduction on standards of proteins, (2) identification of endogenous adduction targets, and (3) quantification of adducted blood proteins as exposure index. The reactivity and outcome of CQ adduction are discussed with emphases on endogenous species, such as dopamine and catechol estrogens. Limitations and advancements in sample preparation, MS instrumentation, and software to facilitate protein adductomics are also discussed.
儿茶酚醌（CQ）基序存在于许多内源性代谢产物、食物、药物和环境污染物等具有生物学相关性的分子中。CQ衍生物可能会发生迈克尔加成反应，并且已被证明能与蛋白质的半胱氨酸、赖氨酸或组氨酸残基的亲核位点形成共价键。CQ加合的蛋白质可能表现出细胞毒性或与其未加合形式不同的生物学功能。识别、表征和定量相关蛋白质靶点是至关重要但具有挑战性的目标。质谱（MS）非常适合用于蛋白质及蛋白质修饰的分析。自下而上蛋白质组学的技术发展极大地推动了生物分子质谱领域的发展，包括蛋白质加合物组学。本综述聚焦于生物分子质谱在以下方面的应用：（1）对蛋白质标准品上CQ加合进行结构和功能表征；（2）识别内源性加合靶点；（3）将加合的血液蛋白质定量作为暴露指标。文中重点讨论了多巴胺和儿茶酚雌激素等内源性物质的CQ加合反应活性及结果。还讨论了样品制备、质谱仪器和软件在促进蛋白质加合物组学方面的局限性和进展。
