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

doi:10.1093/nar/gkac703

HFCAS OpenIR

	A photochemically covalent lock stabilizes aptamer conformation and strengthens its performance for biomedicine
	Zhou, Fang 1,2; Wang, Peng 1,2; Chen, Jianghuai 1; Zhu, Zhijia 1; Li, Youshan 1; Wang, Sujuan 1; Wu, Shanchao 1; Sima, Yingyu 1; Fu, Ting 1,2; Tan, Weihong 1,2,3,4; Zhao, Zilong 1
	2022-08-22
发表期刊	NUCLEIC ACIDS RESEARCH
ISSN	0305-1048
通讯作者	Zhao, Zilong(zlzhao@hnu.edu.cn)
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] .
DOI	10.1093/nar/gkac703
关键词[WOS]	INTERSTRAND CROSS-LINKS ; CANCER ; RECOGNITION ; PROTEIN ; PROBES ; SELECTION
收录类别	SCI
语种	英语
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]
项目资助者	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
WOS研究方向	Biochemistry & Molecular Biology
WOS类目	Biochemistry & Molecular Biology
WOS记录号	WOS:000842622500001
出版者	OXFORD UNIV PRESS
引用统计	被引频次：11[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.hfcas.ac.cn:8080/handle/334002/131992
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.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 2.Chinese Acad Sci, Univ Chinese Acad Sci, Zhejiang Canc Hosp, Inst Basic Med & Canc IBMC,Canc Hosp, 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.Shanghai Jiao Tong Univ, Coll Chem & Chem Engn, Shanghai 200240, 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).