Department of Pharmaceutical Chemistry and the Cardiovascular Research Institute, University of California San Francisco, San Francisco, California, USA.
Protein Sci. 2022 Feb;31(2):312-322. doi: 10.1002/pro.4228. Epub 2021 Nov 16.
To expand protein's covalent bonding ability, latent bioreactive unnatural amino acids have been designed and genetically encoded into proteins, which react with specific natural amino acid residues through proximity-enabled bioreactivity. The resultant new covalent bonds can be selectively created within and between proteins in vitro, in cells, and in vivo. Offering diverse properties previously unattainable, these covalent linkages have been harnessed to enhance protein properties, to modulate protein function, to probe ligand-receptor binding, to identify elusive protein interactions, and to develop covalent protein drugs. Selective introduction of covalent bonds into proteins is affording novel avenues for biological studies, synthetic biology, and biotherapeutics.
为了扩大蛋白质的共价键结合能力，设计并遗传编码了潜伏生物反应性非天然氨基酸，这些氨基酸通过邻近生物反应性与特定的天然氨基酸残基反应。由此产生的新共价键可以在体外、细胞内和体内选择性地在蛋白质内部和之间形成。这些共价键提供了以前无法获得的多种性质，已被用于增强蛋白质性质、调节蛋白质功能、探测配体-受体结合、识别难以捉摸的蛋白质相互作用以及开发共价蛋白质药物。选择性地将共价键引入蛋白质中，为生物学研究、合成生物学和生物治疗提供了新的途径。
