肽
化学
邻苯二甲醛
半胱氨酸
胺气处理
电泳剂
分子内力
亚胺
硫醇
组合化学
氨基酸
残留物(化学)
阳离子聚合
烷基
立体化学
有机化学
衍生化
生物化学
催化作用
高效液相色谱法
酶
作者
Bo Li,Lan Wang,Xiangxiang Chen,Xin Chu,Haoyu Tang,Jie Zhang,Gang He,Li Li,G. Chen
标识
DOI:10.1038/s41467-022-27985-7
摘要
Peptide modification methods that do not rely on the cysteine residue are underdeveloped, and their development could greatly expand the current toolbox for peptide chemistry. During the course of preliminary investigations into the classical ortho-phthalaldehyde (OPA)-amine-thiol condensation reaction, we found that in the absence of thiol, OPA readily condenses with two primary alkyl amines to form a class of underexplored isoindolin-1-imine compounds under mild aqueous conditions. From the intramolecular version of this OPA-2amines reaction, an efficient and selective methodology using mild reaction conditions has been developed for stapling unprotected peptides via crosslinking of two amino groups in both an end-to-side and side-to-side fashion. The stapling method is superfast and broadly applicable for various peptide substrates with the reacting amino groups separated by a wide range of different amino acid units. The macrocyclization reactions of selected substrates are completed within 10 seconds at 5 mM concentration and within 2 minutes at 50 μM concentration. Importantly, the resulting cyclized peptides with an isoindolinimine linkage can be extended in a one-pot sequential addition manner with several different electron-deficient π electrophiles, thereby generating more complex structures.
科研通智能强力驱动
Strongly Powered by AbleSci AI