Synthesis of Polypeptides with High-Fidelity Terminal Functionalities under NCA Monomer-Starved Conditions  

作　　者：Lei Li Jie Cen Wenhao Pan Yuben Zhang Xuanxi Leng Zhengqi Tan Hao Yin Shiyong Liu 

机构地区：[1]Hefei National Laboratory for Physical Sciences at the Microscale,Department of Polymer Science and Engineering,School of Chemistry and Materials Science,University of Science and Technology of China,Hefei,Anhui 230026,China [2]Mass Spectrometry Lab,Hefei National Laboratory for Physical Sciences at the Microscale,University of Science and Technology of China,Hefei,Anhui 230026,China

出　　处：《Research》2022年第1期261-276,共16页研究（英文）

基　　金：support from the National Key R&D Program of China(2020YFA0710700);National Natural Science Foundation of China(NNSFC)Project(51690150,51690154,U19A2094,and 52021002)is gratefully acknowledged.

摘　　要：Controlled polypeptide synthesis viaα-amino acid N-carboxylic anhydride(NCA)polymerization using conventional primary amine initiators encounters two major obstacles:(i)normal amine mechanism(NAM)and activated monomer mechanism(AMM)coexist due to amine basicity and nucleophilicity and(ii)NCA is notoriously sensitive towards moisture and heat and unstable upon storage.We serendipitously discover that N-phenoxycarbonyl-functionalizedα-amino acid(NPCA),a latent NCA precursor,could be polymerized solely based on NAM with high initiating efficiency by using primary amine hydrochloride as an initiator.The polymerization affords well-defined polypeptides with narrow polydispersity and highfidelity terminal functionalities,as revealed by the clean set of MALDI-TOF MS patterns.We further demonstrate successful syntheses of random and block copolypeptides,even under open-vessel conditions.Overall,the integration of moistureinsensitive and air-tolerant NPCA precursors with stable primary amine hydrochloride initiators represents a general strategy for controlled synthesis of high-fidelity polypeptides with sophisticated functions.

关 键 词：functions INITIATOR POLYMERIZATION 

分 类 号：O62[理学—有机化学]