Redwood Bioscience, Burlingame, CA 94010, USA.
Curr Opin Chem Biol. 2010 Dec;14(6):790-6. doi: 10.1016/j.cbpa.2010.09.020. Epub 2010 Oct 26.
In the past decade, numerous chemical technologies have been developed to allow the site-specific post-translational modification of proteins. Traditionally covalent chemical protein modification has been accomplished by the attachment of synthetic groups to nucleophilic amino acids on protein surfaces. These chemistries, however, are rarely sufficiently selective to distinguish one residue within a literal sea of chemical functionality. One solution to this problem is to introduce a unique chemical handle into the target protein that is orthogonal to the remainder of the proteome. In practice, this handle can be a novel peptide sequence, which forms a 'tag' that is selectively and irreversibly modified by enzymes. Furthermore, if the enzymes can tolerate substrate analogs, it becomes possible to engineer chemically modified proteins in a site-specific fashion. This review details the significant progress in creating techniques for the chemoenzymatic generation of protein-small molecule constructs and provides examples of novel applications of these methodologies.
在过去的十年中，已经开发出许多化学技术来实现蛋白质的定点翻译后修饰。传统上，通过将合成基团连接到蛋白质表面的亲核氨基酸上来完成共价化学蛋白质修饰。然而，这些化学方法很少具有足够的选择性来区分字面意义上的化学功能海洋中的一个残基。解决此问题的一种方法是在目标蛋白中引入独特的化学接头，该接头与其余蛋白质组正交。实际上，该接头可以是形成“标签”的新颖肽序列，该标签可被酶选择性和不可逆地修饰。此外，如果酶可以容忍底物类似物，则可以以定点方式工程化学修饰的蛋白质。这篇综述详细介绍了在化学酶促生成蛋白质-小分子构建体方面取得的重大进展，并提供了这些方法的新颖应用实例。
