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Harnessing acylhydrazone-oxime exchange reaction to achieve diverse synthesis of glycosite-specific antibody-drug conjugates

文献类型：期刊论文

作者Xia, Fei1,2,4,9; Liu, Zhi7,8,9; Hang, Jiaying4,9; Xu, Hao6; Xiao, Yuting5; Niu, Shuyue5; Qin, Ji4,10; Lou, Songyue4,10; Liu, Bo9,10; Tang, Feng9,10
刊名ORGANIC & BIOMOLECULAR CHEMISTRY
出版日期2024-12-23
页码9
ISSN号1477-0520
DOI10.1039/d4ob01826e
英文摘要Glycosite-specific antibody-drug conjugates (gsADCs), which carry cytotoxic payloads at the conserved N-glycosylation site, N297, of an IgG, have emerged as a promising ADC format with better therapeutic index. Conjugating the payloads via aldehyde-based chemistry is more friendly to IgGs, and has been widely investigated. However, the efficiency of introducing an aldehyde tag at the N297 site is poor due to the complicated procedures required, such as the multiple-enzyme-catalyzed IgG glycoengineering process and the successive oxidation step, which always results in heterogeneous products and poor stability. Herein, we report an efficient approach to assemble aldehyde-based gsADCs, in which the aldehyde group is first protected by hydrazine and conjugates linker-payloads via an acylhydrazone-oxime exchange reaction. This method exhibits remarkable coupling efficiency to various linker-payloads, and the corresponding gsADCs demonstrate good homogeneity, stability, and in vitro and in vivo efficacy.
WOS关键词MONOCLONAL-ANTIBODY ; IGG ; HYDRAZONE ; BIOCONJUGATION ; GLYCOSYLATION
资助项目National Science Fund for Distinguished Young Scholars[82325045] ; National Science Fund for Distinguished Young Scholars[82204183] ; National Science Fund for Distinguished Young Scholars[22277126] ; National Science Foundation of China (NSFC)[22YF1457400] ; Shanghai Sail Program[TD2020005] ; Hangzhou Innovation and Entrepreneurship Leading Team Project
WOS研究方向Chemistry
语种英语
WOS记录号WOS:001390037300001
出版者ROYAL SOC CHEMISTRY
源URL[http://119.78.100.183/handle/2S10ELR8/315552]  
专题新药研究国家重点实验室
通讯作者Huang, Wei; Yang, Yang; Shi, Wei
作者单位1.Peking Union Med Coll, Sch Basic Med, Beijing 100005, Peoples R China
2.Chinese Acad Med Sci, Peking Union Med Coll, Inst Basic Med Sci, Beijing 100005, Peoples R China
3.Shanghai GlycanLink Biotech Co Ltd, Shanghai 201210, Peoples R China
4.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
5.Shenyang Pharmaceut Univ, Sch Pharm, Shenyang 110016, Peoples R China
6.Nanjing Univ Chinese Med, Sch Chinese Mat Med, 138 Xianlin Rd, Nanjing 210023, Peoples R China
7.ShanghaiTech Univ, Sch Phys Sci & Technol, Shanghai 201210, Peoples R China
8.Lingang Lab, Shanghai 200031, Peoples R China
9.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
10.Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China
推荐引用方式
GB/T 7714		 Xia, Fei,Liu, Zhi,Hang, Jiaying,et al. Harnessing acylhydrazone-oxime exchange reaction to achieve diverse synthesis of glycosite-specific antibody-drug conjugates[J]. ORGANIC & BIOMOLECULAR CHEMISTRY,2024:9.
APA Xia, Fei.,Liu, Zhi.,Hang, Jiaying.,Xu, Hao.,Xiao, Yuting.,...&Shi, Wei.(2024).Harnessing acylhydrazone-oxime exchange reaction to achieve diverse synthesis of glycosite-specific antibody-drug conjugates.ORGANIC & BIOMOLECULAR CHEMISTRY,9.
MLA Xia, Fei,et al."Harnessing acylhydrazone-oxime exchange reaction to achieve diverse synthesis of glycosite-specific antibody-drug conjugates".ORGANIC & BIOMOLECULAR CHEMISTRY (2024):9.

入库方式： OAI收割

来源：上海药物研究所

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