Ren Haiyan
Division of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu 610041, China.
Biochem Soc Trans. 2020 Aug 28;48(4):1807-1817. doi: 10.1042/BST20200508.
There has been a large amount of interest in the development of genetically encoded cross-linkers that target functional groups naturally present in cells. Recently, a new class of unnatural amino acids that specifically react with target residues were developed and genetically incorporated. The selective reaction shows higher cross-linking efficiency, lower background and predictable cross-linking sites. It has been applied to enhance protein/peptide stability, pinpoint protein-protein interactions, stabilize protein complexes, engineer covalent protein inhibitors, identify phosphatases in living cells, etc. These new covalent linkages provide excellent new tools for protein engineering and biological studies. Their applications in biotherapy will provide considerable opportunities for innovating and improving biomolecular medicines.
人们对开发靶向细胞中天然存在的官能团的基因编码交联剂产生了浓厚兴趣。最近，一类能与目标残基特异性反应的新型非天然氨基酸被开发出来并通过基因手段引入。这种选择性反应显示出更高的交联效率、更低的背景以及可预测的交联位点。它已被应用于提高蛋白质/肽的稳定性、精准确定蛋白质-蛋白质相互作用、稳定蛋白质复合物、设计共价蛋白质抑制剂、识别活细胞中的磷酸酶等。这些新的共价连接为蛋白质工程和生物学研究提供了出色的新工具。它们在生物治疗中的应用将为创新和改进生物分子药物提供大量机会。
