A photochemically covalent lock stabilizes aptamer conformation and strengthens its performance for biomedicine
文献类型：期刊论文
| 作者 | Zhou, Fang3,4; Wang, Peng3,4; Chen, Jianghuai4; Zhu, Zhijia4; Li, Youshan4; Wang, Sujuan4; Wu, Shanchao4; Sima, Yingyu4; Fu, Ting3,4; Tan, Weihong1,2,3,4 |
| 刊名 | NUCLEIC ACIDS RESEARCH
 |
| 出版日期 | 2022-08-22 |
| ISSN号 | 0305-1048 |
| DOI | 10.1093/nar/gkac703 |
| 通讯作者 | Zhao, Zilong(zlzhao@hnu.edu.cn) |
| 英文摘要 | Aptamers' vast conformation ensemble consisting of interconverting substates severely impairs their performance and applications in biomedicine. Therefore, developing new chemistries stabilizing aptamer conformation and exploring the conformation-performance relationship are highly desired. Herein, we developed an 8-methoxypsoralen-based photochemically covalent lock to stabilize aptamer conformation via crosslinking the inter-stranded thymine nucleotides at TpA sites. Systematical studies and molecular dynamics simulations were performed to explore the conformation-performance relationship of aptamers, revealing that conformation-stabilized aptamers displayed better ability to bind targets, adapt to physiological environment, resist macrophage uptake, prolong circulation half-life, accumulate in and penetrate into tumor than their counterparts. As expected, conformation-stabilized aptamers efficiently improved the therapeutic efficacy of aptamer-drug conjugation on tumor-bearing mice. Collectively, our study has developed a general, simple and economic strategy to stabilize aptamer conformation and shed light on the conformation- performance relationship of aptamers. laying a basis for promoting their basic researches and applications in biomedicine. [GRAPHICS] . |
| WOS关键词 | INTERSTRAND CROSS-LINKS ; CANCER ; RECOGNITION ; PROTEIN ; PROBES ; SELECTION |
| 资助项目 | National Natural Science Foundation of China[21890744] ; National Natural Science Foundation of China[21974040] ; National Natural Science Foundation of China[22177028] ; China National Postdoctoral Program for Innovative Talents[BX20220309] ; State Key Lab-oratory of Chemo/Biosensing and Chemometrics and Hunan University[21974040] |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000842622500001 |
| 出版者 | OXFORD UNIV PRESS |
| 资助机构 | National Natural Science Foundation of China ; China National Postdoctoral Program for Innovative Talents ; State Key Lab-oratory of Chemo/Biosensing and Chemometrics and Hunan University |
| 源URL | [http://ir.hfcas.ac.cn:8080/handle/334002/131991]  |
| 专题 | 中国科学院合肥物质科学研究院 |
| 通讯作者 | Zhao, Zilong |
| 作者单位 | 1.Shanghai Jiao Tong Univ, Coll Chem & Chem Engn, Shanghai 200240, Peoples R China 2.Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Inst Mol Med IMM, Shanghai 200240, Peoples R China 3.Chinese Acad Sci, Univ Chinese Acad Sci, Zhejiang Canc Hosp, Inst Basic Med & Canc IBMC,Canc Hosp, Hangzhou 310022, Zhejiang, Peoples R China 4.Hunan Univ, Mol Sci & Biomed Lab MBL, State Key Lab Chemo Biosensing & Chemometr, Coll Chem & Chem Engn,Aptamer Engn Ctr Hunan Prov, Changsha 410082, Hunan, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhou, Fang,Wang, Peng,Chen, Jianghuai,et al. A photochemically covalent lock stabilizes aptamer conformation and strengthens its performance for biomedicine[J]. NUCLEIC ACIDS RESEARCH,2022. |
| APA | Zhou, Fang.,Wang, Peng.,Chen, Jianghuai.,Zhu, Zhijia.,Li, Youshan.,...&Zhao, Zilong.(2022).A photochemically covalent lock stabilizes aptamer conformation and strengthens its performance for biomedicine.NUCLEIC ACIDS RESEARCH. |
| MLA | Zhou, Fang,et al."A photochemically covalent lock stabilizes aptamer conformation and strengthens its performance for biomedicine".NUCLEIC ACIDS RESEARCH (2022). |
入库方式： OAI收割
来源：合肥物质科学研究院
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