Chemical Synthesis of Proteins Containing 300 Amino Acids  

作　　者：ZHANG Baochang LI Yulei SHI Weiwei WANG Tongyue ZHANG Feng LIU Lei 

机构地区：[1]Tsinghua-Peking Center for Life Sciences,Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology(Ministry of Education),Center for Synthetic and Systems Biology,State Key Laboratory of Chemical Oncogenomics(Shenzhen),Department of Chemistry,Tsinghua University,Beijing 100084,P.R.China

出　　处：《Chemical Research in Chinese Universities》2020年第5期733-747,共15页高等学校化学研究（英文版）

基　　金：Supported by the National Key R&D Program of China(No.2017YFA0505200);the National Natural Science Foundation of China(Nos.21532004,91753205,81621002).

摘　　要：Chemical synthesis of proteins containing up to 300 amino acids may cover 30%—50%of all the proteins encountered in biomedical studies and may provide an alternate approach to the usually used recombinant expression teclmology,vastly expanding the chemical space of the latter.In the present review article,we tried to survey the recent progresses made for more rapid synthesis of increasingly long peptides and more efficient ligation of multiple peptide segments.The developments of seminal methods by many research groups have greatly contributed to the recent breakthroughs in the successful total synthesis of a number of functionally important proteins,such as oligoubiquitins,bacterial GroEL/ES chaperones,and mirror-image DNA polymerases.Through these studies,a potential bottleneck has also been recognized for the chemical synthesis of large proteins,namely,how to ensure that each peptide segment from a large protein avoids unfavorable aggregation when dissolved in aqueous solution.Many new methods,such as removable backbone modification(RBM)strategy have been developed to overcome this bottleneck,while more studies need to be carried out to develop more effective and less costly methods that ultimately,may lead to fully automatable chemical synthesis of customized proteins of 300 amino acids bearing any artificial designs.

关 键 词：Chemical protein synthesis Solid-phase synthesis PEPTIDE LIGATION 300 amino acid 

分 类 号：O62[理学—有机化学]