中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
Enhanced antibody-defucosylation capability of a-L-fucosidase by proximity-based protein fusion

文献类型：期刊论文

作者Fan, Shuquan2; Li, Wanzhen3; Zhang, Kuixing2; Zou, Xiangman3; Shi, Wei3; Liu, Zhi3; Tang, Caihong3; Huang, Wei1,2,3; Tang, Feng3
刊名BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
出版日期2023-02-19
卷号645页码:40-46
ISSN号0006-291X
DOI10.1016/j.bbrc.2023.01.031
通讯作者Fan, Shuquan(fanshuquan@lcu.edu.cn) ; Huang, Wei(huangwei@simm.ac.cn) ; Tang, Feng(tangfeng2013@simm.ac.cn)
英文摘要Up to date, the reported fucosidases generally show poor activities toward the IgG core-fucose, which limits the efficiency of ENGase-catalyzed glycoengineering process. However, EndoS or EndoS2 owns excellent activity and great selectivity towards the N-glycosylation of IgGs, and their non-catalytic domains are deduced to have specific interactions to IgG Fc domain that result in the great activity and selectivity. Herein, we constructed a series fusion protein of AlfC (an a-L-fucosidase from Lactobacillus casei BL23) with EndoS/S2 non-catalytic domain by replacing the catalytic GH (glycan hydrolase) domain of EndoS/S2 with the AlfC. We found that all these fused AlfCs showed significantly enhanced defucosylation activity toward the deglycosylated IgGs (Fuca1,6GlcNAc-IgG). We also performed the kinetic study of these fusion enzymes, and our results tend to tell that the EndoS-based fusion proteins have higher kcat values while the EndoS2-based ones possess lower Km values other than higher kcat. Conclusively, our research provides an effective approach to improve the activity of AlfC and remarkably shortened the defucosylation process within several minutes, which will significantly promote the development of glycoengineered antibodies in the future.
WOS关键词NONFUCOSYLATED THERAPEUTIC ANTIBODIES ; MONOCLONAL-ANTIBODIES ; NEXT-GENERATION ; IGG ANTIBODIES ; GLYCOSYLATION ; IMPACT ; SPECIFICITY ; BINDING ; FUCOSE ; ENDOS
资助项目National Natural Science Foundation of China (NSFC)[31900914] ; National Natural Science Foundation of China (NSFC)[21877116] ; National Natural Science Foundation of China (NSFC)[92153301] ; National Natural Science Foundation of China (NSFC)[82003574] ; National Key Research and Development Plan grants[2021YEE0200500] ; Natural Science Founda- tion of Shandong Province[LG-QS-202206-03] ; Lingang Laboratory ; [ZR2017BC062]
WOS研究方向Biochemistry & Molecular Biology ; Biophysics
语种英语
出版者ACADEMIC PRESS INC ELSEVIER SCIENCE
WOS记录号WOS:000924677700001
源URL[http://119.78.100.183/handle/2S10ELR8/303370]  
专题中国科学院上海药物研究所
通讯作者Fan, Shuquan; Huang, Wei; Tang, Feng
作者单位1.Univ Chinese Acad Sci, Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China
2.Liaocheng Univ, Sch Life Sci, 1 Hunan Rd, Liaocheng 252000, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Ctr Excellence Mol Cell Sci, Ctr Biotherapeut Discovery Res,CAS Key Lab Recepto, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Fan, Shuquan,Li, Wanzhen,Zhang, Kuixing,et al. Enhanced antibody-defucosylation capability of a-L-fucosidase by proximity-based protein fusion[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2023,645:40-46.
APA Fan, Shuquan.,Li, Wanzhen.,Zhang, Kuixing.,Zou, Xiangman.,Shi, Wei.,...&Tang, Feng.(2023).Enhanced antibody-defucosylation capability of a-L-fucosidase by proximity-based protein fusion.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,645,40-46.
MLA Fan, Shuquan,et al."Enhanced antibody-defucosylation capability of a-L-fucosidase by proximity-based protein fusion".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 645(2023):40-46.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。