Satoh Takumi, Lipton Stuart A
Department of Welfare Engineering, Faculty of Engineering, Iwate University, Morioka 020-8551, Japan.
Trends Neurosci. 2007 Jan;30(1):37-45. doi: 10.1016/j.tins.2006.11.004. Epub 2006 Nov 29.
The importance of phosphorylation of key threonine, serine and tyrosine residues is a well known essential feature of many signal transduction pathways. A similar, highly conserved redox reaction involving cysteine thiols is now emerging as an important regulator of protein function. An example of this redox regulation is S-nitrosylation (the transfer of a nitric oxide group to a key protein thiol). Here, we review the chemical biology of an additional class of drugs, electrophiles (electron-deficient carbon centers), that react with key protein thiols, and provide insights into a broader class of reactions implicated in redox signaling. Interestingly, certain electrophilic compounds, including endogenous metabolites and natural products, seem to have neuroprotective effects, and this has resulted in the development of neuroprotective electrophilic drugs, including prostaglandin derivatives and hydroquinones, that exert their action through activating antioxidant-signaling cascades.
关键苏氨酸、丝氨酸和酪氨酸残基的磷酸化作用十分重要，这是许多信号转导途径中众所周知的基本特征。现在，一种涉及半胱氨酸硫醇的类似且高度保守的氧化还原反应正逐渐成为蛋白质功能的重要调节因子。这种氧化还原调节的一个例子是S-亚硝基化（将一氧化氮基团转移到关键蛋白质硫醇上）。在此，我们综述了另一类药物——亲电试剂（缺电子碳中心）的化学生物学，这类试剂可与关键蛋白质硫醇发生反应，并深入探讨了与氧化还原信号传导相关的更广泛的反应类别。有趣的是，某些亲电化合物，包括内源性代谢物和天然产物，似乎具有神经保护作用，这促使了神经保护性亲电药物的研发，包括前列腺素衍生物和对苯二酚，它们通过激活抗氧化信号级联反应发挥作用。
