journal article·2020-07-28

Programming Biomimetically Confined Aptamers with DNA Frameworks

Xiuhai Mao, Mengmeng Liu, Lei Yan, Mengying Deng, Fan Li, Min Li, Fei Wang, Jiang Li, Lihua Wang, Yang Tian, Chunhai Fan, Xiaolei Zuo

ACS Nano· Volume 14· Issue 7
Publisher page

Abstract

Active sites of proteins are generally encapsulated within three-dimensional peptide scaffolds that provide the molecular-scale confinement microenvironment. Nevertheless, the ability to tune thermodynamic stability in biomimetic molecular confinement relies on the macromolecular crowding effect of lack of stoichiometry and reconfigurability. Here, we report a framework nucleic acid (FNA)-based strategy to increase thermodynamic stability of aptamers. We demonstrate that the molecular-scale confinement increases the thermodynamic stability of aptamers via facilitated folding kinetics, which is confirmed by the single-molecule FRET (smFRET). Unfavorable conformations of aptamers are restricted as revealed by the Monte Carlo simulation. The binding affinity of the DNA framework-confined aptamer is improved by ∼3-fold. With a similar strategy we improve the catalytic activity of hemin-binding aptamer. Our approach thus shows high potential for designing protein-mimicking DNA nanostructures with enhanced binding affinity and catalytic activity for biosensing and biomedical engineering.
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Research context

OpenAlex topics: Advanced biosensing and bioanalysis techniques · RNA Interference and Gene Delivery · DNA and Nucleic Acid Chemistry

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China

Shanghai Key Laboratory of Green Chemistry and Chemical Processes, Department of Chemistry, School of Chemistry and Molecular Engineering, East China Normal University, Dongchuan Road 500, Shanghai 200241, China

Division of Physical Biology, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China

Bioimaging Center, Shanghai Synchrotron Radiation Facility, Zhangjiang Laboratory, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210, China

Joint Research Center for Precision Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital South Campus, Southern Medical University Affiliated Fengxian Hospital, Shanghai 201499, China

School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Institute of Translational Medicine, Shanghai Jiao Tong University,, Shanghai 200240, China

Funding

Ministry of Science and Technology of the People's Republic of China · China Postdoctoral Science Foundation · Shanghai Municipal Education Commission · National Natural Science Foundation of China · Shanghai Education Development Foundation · Innovative Research Team of High Level Local Universities in Shanghai

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