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One-Pot Assembly of Dual-Site-Specific Antibody–Drug Conjugates via Glycan Remodeling and Affinity-Directed Traceless Conjugation

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成果类型:
期刊论文
作者:
Tang, Caihong;Zeng, Yue;Zhang, Jianxin;Zheng, Xing;Tang, Feng;...
通讯作者:
Yao, X.;Jiang, Z.-X.;Huang, W.;Shi, W.
作者机构:
[Tang, Caihong; Jiang, Zhong-Xing; Yao, Xu; Zheng, Xing] Univ South China, Inst Pharm & Pharmacol, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.
[Zhang, Jianxin; Tang, Feng; Shi, Wei; Zeng, Yue; Tang, Caihong; Huang, Wei] Chinese Acad Sci, Shanghai Inst Mat Med, CAS Ctr Excellence Mol Cell Sci, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China.
[Shi, Wei; Huang, Wei] Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China.
[Huang, Wei] Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China.
[Huang, Wei] Univ Chinese Acad Sci, Beijing 100049, Peoples R China.
通讯机构:
[Xu Yao; Zhong-Xing Jiang] I
[Wei Shi; Wei Huang] C
CAS Key Laboratory of Receptor Research, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, No. 555 Zuchongzhi Road, Pudong, Shanghai 201203, China<&wdkj&>School of Pharmaceutical Science and Technology, Hangzhou Institute of Advanced Study, Hangzhou 310024, China<&wdkj&>School of Chinese Materia Medica, Nanjing University of Chinese Medicine, No. 138 Xianlin Road, Nanjing 210023, China<&wdkj&>University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China<&wdkj&>Shanghai GlycanLink Biotech. Co. Ltd., Minhang, Shanghai 201203, China<&wdkj&>Institute of Pharmacy and Pharmacology, Hengyang Medicinal School, University of South China, Hengyang, Hunan 421001, China<&wdkj&>CAS Key Laboratory of Receptor Research, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, No. 555 Zuchongzhi Road, Pudong, Shanghai 201203, China<&wdkj&>School of Pharmaceutical Science and Technology, Hangzhou Institute of Advanced Study, Hangzhou 310024, China
语种:
英文
期刊:
Bioconjugate Chemistry
ISSN:
1043-1802
年:
2023
卷:
34
期:
4
页码:
748-755
基金类别:
This work was supported by the Natural Science Foundation of China (NSFC, No. 82204183, 92153301, 82003574, and 22277126), Shanghai Sail Program (No. 22YF1457400), the Special Research Assistant Program (Chinese Academy of Sciences, CAS, to W.S.), the China Postdoctoral Science Foundation (No. 2021M700158), Shanghai Postdoctoral Excellence Program (No. 2021428), the Laboratory of Tea and Health of Heng-yang (202150083704), and the Undergraduate Research Learning and Innovative Experiment Project (X202110555454, X202110555467, X202110555473, 220XCX105, 220XCX310, and 220XCX294).
机构署名:
本校为第一机构
院系归属:
药学与生物科学学院
摘要:
The drug-to-antibody ratio (DAR) value and dual-drug combination greatly influence the therapeutic index of antibody–drug conjugates (ADCs). The reported approaches usually require multifunctional branched linkers, a combination of complicated technologies, or protein–protein ligation, which may incorporate multihydrophobic fragments or result in low coupling efficiency. Herein, we developed a facile and efficient one-pot method to assemble dual-site-specific ADCs with defined DARs at both the N-glycosylation site and K248 site, either with t...

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