Department of Chemistry, University of California, Berkeley, Berkeley, California, USA.
Materials Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA..
Nat Chem Biol. 2017 Jul;13(7):697-705. doi: 10.1038/nchembio.2416. Epub 2017 Jun 20.
The formation of well-defined protein bioconjugates is critical for many studies and technologies in chemical biology. Tried-and-true methods for accomplishing this typically involve the targeting of cysteine residues, but the rapid growth of contemporary bioconjugate applications has required an expanded repertoire of modification techniques. One very powerful set of strategies involves the modification of proteins at their N termini, as these positions are typically solvent exposed and provide chemically distinct sites for many protein targets. Several chemical techniques can be used to modify N-terminal amino acids directly or convert them into unique functional groups for further ligations. A growing number of N-terminus-specific enzymatic ligation strategies have provided additional possibilities. This Perspective provides an overview of N-terminal modification techniques and the chemical rationale governing each. Examples of specific N-terminal protein conjugates are provided, along with their uses in a number of diverse biological applications.
形成定义明确的蛋白质生物缀合物对于化学生物学中的许多研究和技术至关重要。实现这一目标的经过验证的方法通常涉及半胱氨酸残基的靶向，但当代生物缀合物应用的快速发展需要扩展修饰技术的 repertoire。一组非常强大的策略涉及蛋白质在其 N 末端的修饰，因为这些位置通常暴露在溶剂中，并且为许多蛋白质靶标提供了化学上不同的位点。几种化学技术可用于直接修饰 N 末端氨基酸，或将其转化为独特的功能基团以进行进一步连接。越来越多的 N 末端特异性酶连接策略提供了更多的可能性。本观点提供了 N 末端修饰技术及其每种技术的化学原理的概述。提供了特定 N 末端蛋白质缀合物的实例及其在许多不同生物学应用中的用途。
