A photochemically covalent lock stabilizes aptamer conformation and strengthens its performance for biomedicine

doi:10.1093/nar/gkac703

	A photochemically covalent lock stabilizes aptamer conformation and strengthens its performance for biomedicine
	Zhou, Fang 3,4; Wang, Peng 3,4; Chen, Jianghuai 4; Zhu, Zhijia 4; Li, Youshan 4; Wang, Sujuan 4; Wu, Shanchao 4; Sima, Yingyu 4; Fu, Ting 3,4; Tan, Weihong 1,2,3,4
刊名	NUCLEIC ACIDS RESEARCH
	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] .
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关键词	INTERSTRAND CROSS-LINKS ; CANCER ; RECOGNITION ; PROTEIN ; PROBES ; SELECTION
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	OXFORD UNIV PRESS
WOS记录号	WOS:000842622500001
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
内容类型	期刊论文
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).