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Chemical Synthesis of Native ADP-Ribosylated Oligonucleotides Enables Analysis of DNA ADP-Ribosylation Hydrolase Specificity

文献类型：期刊论文

作者Tang, Li2,3,4; Lu, Yang5; van der Heijden, Femke L. A. M.1; Chen, Yanrong3,6; Jiang, Shuyan3,7; Meeuwenoord, Nico J.1; Liu, Lingxiao3,8; Yu, Zongxing3,8; Chen, Zhenrong2,3,4; Schuller, Marion5
刊名JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
出版日期2026-01-08
页码13
ISSN号0002-7863
DOI10.1021/jacs.5c17532
通讯作者Filippov, Dmitri V.(filippov@lic.leidenuniv.nl) ; Ahel, Ivan(ivan.ahel@path.ox.ac.uk) ; Liu, Qiang(liuqiang@simm.ac.cn)
英文摘要ADP-ribosylation (ADPr) is a modification by which an ADP-ribose moiety is conjugated to different molecules by ADP-ribosyltransferases (ARTs) to control various cellular processes in organisms from all kingdoms of life. While traditionally considered primarily as a post-translational modification of proteins, recent evidence has demonstrated that ADPr of nucleic acids (DNA and RNA) has emerged as a widespread type of ADPr. However, the precise biological roles and underlying mechanisms remain elusive, largely due to the lack of ADP-ribosylated nucleic acid molecular tools. Inspired by the native thymidine modification sites of ADP-ribosylated DNA, we developed a synthetic method for the chemo- and stereoselective assembly of both anomers of ADP-ribosylated thymidine (T-ADPr). We further tailored our method to successfully synthesize ADP-ribosylated oligonucleotides with desired sequences via an automatic solid-phase synthesis. We used the synthetic ADPr substrates, including the ADP-ribosylated DNA sequence motif TCTC that is targeted by bacterial ARTs to control DNA replication or antiphage response, and showed the utility of newly developed tools to characterize the specificity and mechanism of action of different hydrolases in ADPr reversal.
WOS关键词PROTEIN ; TOXIN ; MONO(ADP-RIBOSYL)ATION ; PIERISIN-1 ; RNA
资助项目Science and Technology Commission of Shanghai Municipality[22PJ1415600] ; Cancer Research UK[C35050/A22284] ; Nederlandse Organisatie voor Wetenschappelijk Onderzoek[OCENW.KLEIN.497] ; National Natural Science Foundation of China[22207114] ; Bureau of Frontier Sciences and Education, Chinese Academy of Sciences[XDB1360000] ; Wellcome Trust[210634] ; Zhongshan Science and Technology Bureau[CXTD2022012] ; Biotechnology and Biological Sciences Research Council[BB/R007195/1]
WOS研究方向Chemistry
语种英语
WOS记录号WOS:001656965000001
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/322560]  
专题中国科学院上海药物研究所
通讯作者Filippov, Dmitri V.; Ahel, Ivan; Liu, Qiang
作者单位1.Leiden Univ, Leiden Inst Chem, Bioorgan Synth, NL-2300 RA Leiden, Netherlands
2.Chinese Acad Sci, Shanghai Inst Mat Med, Carbohydrate Based Drug Res Ctr, Shanghai 201203, Peoples R China
3.Zhongshan Inst Drug Discovery, Zhongshan 528400, Peoples R China
4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
5.Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England
6.Guangzhou Univ Chinese Med, Guangzhou 510006, Peoples R China
7.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China
8.Southern Med Univ, Sch Pharmaceut Sci, Guangzhou 510515, Peoples R China
推荐引用方式
GB/T 7714		 Tang, Li,Lu, Yang,van der Heijden, Femke L. A. M.,et al. Chemical Synthesis of Native ADP-Ribosylated Oligonucleotides Enables Analysis of DNA ADP-Ribosylation Hydrolase Specificity[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,2026:13.
APA Tang, Li.,Lu, Yang.,van der Heijden, Femke L. A. M..,Chen, Yanrong.,Jiang, Shuyan.,...&Liu, Qiang.(2026).Chemical Synthesis of Native ADP-Ribosylated Oligonucleotides Enables Analysis of DNA ADP-Ribosylation Hydrolase Specificity.JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,13.
MLA Tang, Li,et al."Chemical Synthesis of Native ADP-Ribosylated Oligonucleotides Enables Analysis of DNA ADP-Ribosylation Hydrolase Specificity".JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2026):13.

入库方式： OAI收割

来源：上海药物研究所

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