Design and synthesis of enediyne chimeras for targeted degradation of PD-L1
文献类型：期刊论文
| 作者 | Pu, Fangxu2; Li, Xuejie3,4; Yan, Kai1; Cheng, Haonan2; Suo, Wenkai3,4; Xiao, Zhongdang1; Lan, Jiaming3; Hu, Aiguo2 |
| 刊名 | JOURNAL OF MATERIALS CHEMISTRY B
 |
| 出版日期 | 2026-02-04 |
| 页码 | 8 |
| ISSN号 | 2050-750X |
| DOI | 10.1039/d5tb02369f |
| 通讯作者 | Lan, Jiaming() ; Hu, Aiguo() |
| 英文摘要 | A substantial fraction of human proteins, including secreted and membrane-localized species, are linked to diseases such as cancer and neurodegeneration upon overexpression or misfolding. However, state-of-the-art targeted protein degradation (TPD) strategies targeting these proteins face limitations such as the "hook" effect and interference with normal cell function. Recently, we developed Protein-Radical-Oxidation Targeting Enediyne Chimeras (PROTECs), a TPD platform that employs an enediyne warhead to directly degrade target proteins without requiring cellular organelles for protein degradation. To extend the application scenarios of PROTECs to the extracellular environment, we herein designed Compound-1, a PROTEC molecule incorporating a PD-L1-targeting ligand (BMS-57), an intrinsic enediyne degradation warhead, and sulfate-based hydrophilicity-adjusting groups to enforce extracellular localization. Compound-1 induced potent and selective degradation of membrane PD-L1 in HeLa cells, achieving a half-maximal degradation concentration (DC50) of 44 nM, independent of both proteasomal and lysosomal activity. Furthermore, the targeted PD-L1 degradation reversed tumor immune evasion and enhanced cancer cell killing by peripheral blood mononuclear cells. This study establishes the PROTEC platform as a robust and modular strategy for degrading membrane-associated and extracellular disease-relevant proteins. |
| WOS关键词 | OXIDATION ; PROTACS |
| 资助项目 | Chinese Academy of Sciences[XDB0490000] ; National Natural Science Foundation of China[23141902400] ; National Natural Science Foundation of China[32470158] |
| WOS研究方向 | Materials Science |
| 语种 | 英语 |
| WOS记录号 | WOS:001684372400001 |
| 出版者 | ROYAL SOC CHEMISTRY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/322869]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Lan, Jiaming; Hu, Aiguo |
| 作者单位 | 1.Southeast Univ, Sch Biol Sci & Med Engn, State Key Lab Bioelect, Nanjing 210096, Peoples R China 2.East China Univ Sci & Technol, Sch Mat Sci & Engn, Shanghai Key Lab Adv Polymer Mat, Shanghai 200237, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China 4.Univ Chinese Acad Sci, Beijing 101408, Peoples R China |
| 推荐引用方式 GB/T 7714 | Pu, Fangxu,Li, Xuejie,Yan, Kai,et al. Design and synthesis of enediyne chimeras for targeted degradation of PD-L1[J]. JOURNAL OF MATERIALS CHEMISTRY B,2026:8. |
| APA | Pu, Fangxu.,Li, Xuejie.,Yan, Kai.,Cheng, Haonan.,Suo, Wenkai.,...&Hu, Aiguo.(2026).Design and synthesis of enediyne chimeras for targeted degradation of PD-L1.JOURNAL OF MATERIALS CHEMISTRY B,8. |
| MLA | Pu, Fangxu,et al."Design and synthesis of enediyne chimeras for targeted degradation of PD-L1".JOURNAL OF MATERIALS CHEMISTRY B (2026):8. |
入库方式： OAI收割
来源：上海药物研究所
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