Structure-guided post-SELEX optimization of an ochratoxin A aptamer

doi:10.1093/nar/gkz336

	Structure-guided post-SELEX optimization of an ochratoxin A aptamer
	Xu, Guohua 2; Zhao, Jiajing 2,3; Liu, Na 2,3; Yang, Minghui 2; Zhao, Qiang 1,3; Li, Conggang 2,3; Liu, Maili 2,3
刊名	NUCLEIC ACIDS RESEARCH
	2019-06-20
卷号	47 期号:11 页码:5963-5972
ISSN号	0305-1048
DOI	10.1093/nar/gkz336
英文摘要	SELEX is the cornerstone for aptamer research with broad applications in biosensors and medicine. To improve the affinity of selected aptamers, we propose a structure-guided post-SELEX approach, an optimizationmethod based on the precise secondary structure of the aptamer-ligand complex. We demonstrate this approach using the Ochratoxin A (OTA) aptamer. Guided by the structure, we designed a new aptamer whose affinity is improved by more than 50-fold. We also determined the high-resolution NMR structure of the new aptamer-OTA complex and elucidated the discriminatory recognition mechanism of one atomic difference between two analogs, OTA and OTB. The aptamer forms an unusual hairpin structure containing an intramolecular triple helix, which is not seen in the previously determined aptamer complex. The pi-pi stacking, the hydrophobic interaction, hydrogen bonds and halogen bonds between OTA and the aptamer contribute to the recognition of OTA, and the halogen bonds play an important role in discriminating between OTA and OTB. Our results demonstrate that the structure-guided post-SELEX approach improves aptamers affinity. An improved OTA biosensor system might be developed using this new strategy.
资助项目	Hubei Province[2016CFA002] ; National Natural Sciences Foundation of China[21190041] ; National Natural Sciences Foundation of China[21735007] ; National Natural Sciences Foundation of China[21605157] ; National Natural Sciences Foundation of China[21874149] ; Ministry of Science and Technology of China[2017YFA0505400] ; K.C. Wong Education Foundation ; National Natural Sciences Foundation of China
WOS关键词	DNA APTAMER ; XPLOR-NIH ; NMR ; RECOGNITION ; LIGANDS ; BINDING ; FLUORESCENCE ; ASSIGNMENT ; TOXICITY
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	OXFORD UNIV PRESS
WOS记录号	WOS:000475702000045
资助机构	Hubei Province ; Hubei Province ; National Natural Sciences Foundation of China ; National Natural Sciences Foundation of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; K.C. Wong Education Foundation ; K.C. Wong Education Foundation ; National Natural Sciences Foundation of China ; National Natural Sciences Foundation of China ; Hubei Province ; Hubei Province ; National Natural Sciences Foundation of China ; National Natural Sciences Foundation of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; K.C. Wong Education Foundation ; K.C. Wong Education Foundation ; National Natural Sciences Foundation of China ; National Natural Sciences Foundation of China ; Hubei Province ; Hubei Province ; National Natural Sciences Foundation of China ; National Natural Sciences Foundation of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; K.C. Wong Education Foundation ; K.C. Wong Education Foundation ; National Natural Sciences Foundation of China ; National Natural Sciences Foundation of China ; Hubei Province ; Hubei Province ; National Natural Sciences Foundation of China ; National Natural Sciences Foundation of China ; Ministry of Science and Technology of China ; Ministry of Science and Technology of China ; K.C. Wong Education Foundation ; K.C. Wong Education Foundation ; National Natural Sciences Foundation of China ; National Natural Sciences Foundation of China
内容类型	期刊论文
源URL	[http://ir.wipm.ac.cn/handle/112942/14713]
专题	中国科学院武汉物理与数学研究所
通讯作者	Li, Conggang
作者单位	1.Chinese Acad Sci, Res Ctr Ecoenvironm Sci, State Key Lab Environm Chem & Ecotoxicol, Beijing 100085, Peoples R China 2.Chinese Acad Sci, Key Lab Magnet Resonance Biol Syst,Wuhan Inst Phy, State Key Lab Magnet Resonance & Atom & Mol Phys, Natl Ctr Magnet Resonance Wuhan,Wuhan Natl Lab Op, Wuhan 430071, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100029, Peoples R China
推荐引用方式 GB/T 7714	Xu, Guohua,Zhao, Jiajing,Liu, Na,et al. Structure-guided post-SELEX optimization of an ochratoxin A aptamer[J]. NUCLEIC ACIDS RESEARCH,2019,47(11):5963-5972.
APA	Xu, Guohua.,Zhao, Jiajing.,Liu, Na.,Yang, Minghui.,Zhao, Qiang.,...&Liu, Maili.(2019).Structure-guided post-SELEX optimization of an ochratoxin A aptamer.NUCLEIC ACIDS RESEARCH,47(11),5963-5972.
MLA	Xu, Guohua,et al."Structure-guided post-SELEX optimization of an ochratoxin A aptamer".NUCLEIC ACIDS RESEARCH 47.11(2019):5963-5972.