A Traceless Site-Specific Conjugation on Native Antibodies Enables Efficient One-Step Payload Assembly
文献类型：期刊论文
| 作者 | Zeng, Yue3,4,5; Shi, Wei4,5; Dong, Qian3,4,5; Li, Wanzhen2; Zhang, Jianxin2; Ren, Xuelian1; Tang, Caihong4; Liu, Bo4,5; Song, Yuanli1; Wu, Yali1 |
| 刊名 | ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
 |
| 出版日期 | 2022-07-27 |
| 页码 | 11 |
| 关键词 | Acyl Transfer Anti-Tumor One-Step Synthesis Site-Specific ADCs Thioester |
| ISSN号 | 1433-7851 |
| DOI | 10.1002/anie.202204132 |
| 通讯作者 | Tang, Feng(tangfeng2013@simm.ac.cn) ; Huang, Wei(huangwei@simm.ac.cn) |
| 英文摘要 | Direct chemical modification of native antibodies in a site-specific manner remains a great challenge. Ligand-directed conjugation can achieve the selective modification of antibodies, but usually requires multiple extra steps for ligand release and cargo assembly. Herein, we report a novel, traceless strategy to enable the facile and efficient one-step synthesis of site-specific antibody-drug conjugates (ADCs) by harnessing a thioester-based acyl transfer reagent. The designed reagent, consisting of an optimized Fc-targeting ligand, a thioester bridge and a toxin payload, directly assembles the toxin precisely onto the K251 position of native IgGs and simultaneously self-releases the affinity ligand in one step. With this method, we synthesized a series of K251-linked ADCs from native Trastuzumab. These ADCs demonstrated excellent homogeneity, thermal stability, and both in vitro and in vivo anti-tumor activity. This strategy is equally efficient for IgG1, IgG2, and IgG4 subtypes. |
| WOS关键词 | DRUG CONJUGATION ; NEXT-GENERATION ; GLYCOSYLATION ; STRATEGIES ; CHEMISTRY ; PROTEINS ; IGG |
| 资助项目 | Natural Science Foundation of China (NSFC)[21877116] ; Natural Science Foundation of China (NSFC)[92153301] ; Natural Science Foundation of China (NSFC)[82003574] ; Shanghai Sail Program[19YF1457100] ; Shanghai Sail Program[22YF1457400] ; Shanghai Municipal Science and Technology Major Project, Hangzhou innovation and entrepreneurship leading team project[TD2020005] ; Lingang Laboratory[LG-QS202206-03] ; Special Research Assistant Program (Chinese Academy of Sciences, CAS) |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000830729300001 |
| 出版者 | WILEY-V C H VERLAG GMBH |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/302004]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Tang, Feng; Huang, Wei |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 2.Nanjing Univ Chinese Med, Sch Chinese Mat Med, 138 Xianlin Rd, Nanjing 210023, Peoples R China 3.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China 4.Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 5.Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zeng, Yue,Shi, Wei,Dong, Qian,et al. A Traceless Site-Specific Conjugation on Native Antibodies Enables Efficient One-Step Payload Assembly[J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,2022:11. |
| APA | Zeng, Yue.,Shi, Wei.,Dong, Qian.,Li, Wanzhen.,Zhang, Jianxin.,...&Huang, Wei.(2022).A Traceless Site-Specific Conjugation on Native Antibodies Enables Efficient One-Step Payload Assembly.ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,11. |
| MLA | Zeng, Yue,et al."A Traceless Site-Specific Conjugation on Native Antibodies Enables Efficient One-Step Payload Assembly".ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2022):11. |
入库方式： OAI收割
来源：上海药物研究所
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