Engineering Enzyme-Cleavable Oligonucleotides by Automated Solid-Phase Incorporation of Cathepsin B Sensitive Dipeptide Linkers

doi:10.1002/anie.202114016

	Engineering Enzyme-Cleavable Oligonucleotides by Automated Solid-Phase Incorporation of Cathepsin B Sensitive Dipeptide Linkers
	Jin, Cheng 4; Ei-Sagheer, Afaf H.1,4; Li, Siqi 5; Vallis, Katherine A.5; Tan, Weihong 2,3; Brown, Tom 4
刊名	ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
	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.
资助项目	UK BBSRC[BB/S018794/1]
WOS关键词	ANTIBODY ; CONJUGATE
WOS研究方向	Chemistry
语种	英语
出版者	WILEY-V C H VERLAG GMBH
WOS记录号	WOS:000753680800001
资助机构	UK BBSRC
内容类型	期刊论文
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.Suez Univ, Fac Petr & Min Engn, Dept Sci & Math, Suez 43721, Egypt 2.Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Inst Mol Med IMM, Shanghai 200240, Peoples R China 3.Chinese Acad Sci, Inst Basic Med & Canc IBMC, Zhejiang Canc Hosp, Canc Hosp,Univ Chinese Acad Sci, Hangzhou 310022, Zhejiang, Peoples R China 4.Univ Oxford, Chem Res Lab, Dept Chem, 12 Mansfield Rd, Oxford OX1 3TA, England 5.Univ Oxford, Dept Oncol, Oxford Inst Radiat Oncol, MRC, Oxford OX3 7DQ, England
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).