Site-selective protein-modification chemistry for basic biology and drug development
Site-selective protein-modification chemistry for basic biology and drug development
复制标题
DOI：
10.1038/nchem.2393
复制
发表时间：
2016-02-01
期刊：
影响因子：
21.8
通讯作者：
Bernardes, Goncalo J. L.
中科院分区：
文献类型：
--
作者：
Krall, Nikolaus;da Cruz, Filipa P.;Bernardes, Goncalo J. L.
自然界制造了复杂的机制，在蛋白质在核糖体中合成后，共价使其结构多样化。为了模仿自然，化学家们开发了一大套反应，使蛋白质在预定位置的表达后修饰成为可能。这些反应现在被用来选择性地在蛋白质上安装特定的修饰，以用于许多生物和治疗应用。例如，它们提供了在蛋白质上安装翻译后修饰的机会，以确定其确切的生物学作用。用荧光染料标记活细胞中的蛋白质，可以跟踪蛋白质的摄取和细胞内的运输，还可以用光学方法测量生理参数。通过将有效的细胞毒剂偶联到抗体上，可以获得疗效更好、副作用更少的新型抗癌药物。在这一视角下，我们重点介绍了目前和未来最令人兴奋的化学位点选择性蛋白质修饰的应用，并考虑了要更广泛地使用，仍然需要克服哪些障碍。
Nature has produced intricate machinery to covalently diversify the structure of proteins after their synthesis in the ribosome. In an attempt to mimic nature, chemists have developed a large set of reactions that enable post-expression modification of proteins at pre-determined sites. These reactions are now used to selectively install particular modifications on proteins for many biological and therapeutic applications. For example, they provide an opportunity to install post-translational modifications on proteins to determine their exact biological roles. Labelling of proteins in live cells with fluorescent dyes allows protein uptake and intracellular trafficking to be tracked and also enables physiological parameters to be measured optically. Through the conjugation of potent cytotoxicants to antibodies, novel anti-cancer drugs with improved efficacy and reduced side effects may be obtained. In this Perspective, we highlight the most exciting current and future applications of chemical site-selective protein modification and consider which hurdles still need to be overcome for more widespread use.