Efficient Chemical Synthesis and Folding of Mirror-Image Tropomyosin Receptor Kinase A Using the Strategy of Removable Glycosylation Modification  

作　　者：Tongyue Wang Weiwei Shi Guo-Chao Chu Yi-Ming Li 

机构地区：[1]Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology,Department of Chemistry,Tsinghua University,Beijing 100084,China [2]School of Food and Biological Engineering,Engineering Research Center of Bio-process,Ministry of Education,Key Laboratory of Animal Source of Anhui Province,Hefei University of Technology,Hefei,Anhui 230009,China

出　　处：《Chinese Journal of Chemistry》2024年第19期2316-2322,共7页中国化学（英文版）

基　　金：supported by the National Natural Science Foundation of China(Nos.22227810,22277020,22307061);China Postdoctoral Science Foundation(No.2022M721801);the Beijing Life Science Academy(No.2023000cc0130).

摘　　要：Comprehensive Summary The strategy of removable glycosylation modification was used to overcome the low-efficiency problem encountered in the chemical synthesis of the mirror-image D-version of the immunoglobulin(Ig)-like domain of tropomyosin receptor kinase A(DlgCTrkA),a protein molecule needed for mirror-image screening of D-peptide ligands targeting this cell membrane receptor.It was found that O-linked-β-N-acetyl-D-glucosamine(O-GlcNAc)modification at^(D)Ser^(312),or^(D)Ser^(320)can significantly improve the efficiency of DlgCTrkA synthesis and folding,while O-GlcNAc modification at^(D)Ser^(330)showed barely any improvement.This study provides a new example demonstrating the power of the removable glycosylation modification strategy in the chemical synthesis and folding of difficult-to-obtain proteins.It also presents evidence that removable glycosylation modification at different sites would significantly affect the efficiency of protein folding promoted by this strategy.

关 键 词：Chemical protein synthesis Removable glycosylation modification Synthetic methods Protein folding D-protein 

分 类 号：O62[理学—有机化学]