Engineering Enzyme-Cleavable Oligonucleotides by Automated Solid-Phase Incorporation of Cathepsin B Sensitive Dipeptide Linkers
文献类型：期刊论文
| 作者 | Jin, Cheng1; Ei-Sagheer, Afaf H.1,5; Li, Siqi4; Vallis, Katherine A.4; Tan, Weihong2,3; Brown, Tom1 |
| 刊名 | ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
 |
| 出版日期 | 2022-02-10 |
| 关键词 | Cathepsin B DNA Breakage Dipeptide Linker Oligonucleotide-Drug Conjugates Solid-Phase Synthesis |
| ISSN号 | 1433-7851 |
| DOI | 10.1002/anie.202114016 |
| 通讯作者 | Brown, Tom(tom.brown@chem.ox.ac.uk) |
| 英文摘要 | Oligonucleotides containing cleavable linkers have emerged as versatile tools to achieve stimulus-responsive and site-specific cleavage of DNA. However, the limitations of previously reported cleavable linkers including photolabile and disulfide linkers have restricted their applications in vivo. Inspired by the cathepsin B-sensitive dipeptide linkers in antibody-drug conjugates (ADCs) such as Adcetris, we have developed Val-Ala-02 and Val-Ala-Chalcone phosphoramidites for the automated synthesis of enzyme-cleavable oligonucleotides. Cathepsin B digests Val-Ala-02 and Val-Ala-Chalcone linkers efficiently, enabling cleavage of oligonucleotides into two components or release of small-molecule payloads. Based on the prior success of dipeptide linkers in ADCs, we believe that these dipeptide linker phosphoramidites will promote new clinical applications of therapeutic oligonucleotides. |
| WOS关键词 | ANTIBODY ; CONJUGATE |
| 资助项目 | UK BBSRC[BB/S018794/1] |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000753680800001 |
| 出版者 | WILEY-V C H VERLAG GMBH |
| 资助机构 | UK BBSRC |
| 源URL | [http://ir.hfcas.ac.cn:8080/handle/334002/127533]  |
| 专题 | 中国科学院合肥物质科学研究院 |
| 通讯作者 | Brown, Tom |
| 作者单位 | 1.Univ Oxford, Chem Res Lab, Dept Chem, 12 Mansfield Rd, Oxford OX1 3TA, England 2.Chinese Acad Sci, Inst Basic Med & Canc IBMC, Zhejiang Canc Hosp, Canc Hosp,Univ Chinese Acad Sci, Hangzhou 310022, Zhejiang, Peoples R China 3.Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Inst Mol Med IMM, Shanghai 200240, Peoples R China 4.Univ Oxford, Dept Oncol, Oxford Inst Radiat Oncol, MRC, Oxford OX3 7DQ, England 5.Suez Univ, Fac Petr & Min Engn, Dept Sci & Math, Suez 43721, Egypt |
| 推荐引用方式 GB/T 7714 | Jin, Cheng,Ei-Sagheer, Afaf H.,Li, Siqi,et al. Engineering Enzyme-Cleavable Oligonucleotides by Automated Solid-Phase Incorporation of Cathepsin B Sensitive Dipeptide Linkers[J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,2022. |
| APA | Jin, Cheng,Ei-Sagheer, Afaf H.,Li, Siqi,Vallis, Katherine A.,Tan, Weihong,&Brown, Tom.(2022).Engineering Enzyme-Cleavable Oligonucleotides by Automated Solid-Phase Incorporation of Cathepsin B Sensitive Dipeptide Linkers.ANGEWANDTE CHEMIE-INTERNATIONAL EDITION. |
| MLA | Jin, Cheng,et al."Engineering Enzyme-Cleavable Oligonucleotides by Automated Solid-Phase Incorporation of Cathepsin B Sensitive Dipeptide Linkers".ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2022). |
入库方式： OAI收割
来源：合肥物质科学研究院
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