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Activation of Aptamers with Gain of Function by Small‐Molecule‐Clipping of Intramolecular Motifs
Author(s) -
Huang Mengjiao,
Li Tingyu,
Xu Yuanfeng,
Wei Xinyu,
Song Jia,
Lin Bingqian,
Zhu Zhi,
Song Yanling,
Yang Chaoyong
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202013570
Subject(s) - aptamer , small molecule , clipping (morphology) , nucleic acid , dna , click chemistry , chemistry , biophysics , combinatorial chemistry , biology , biochemistry , genetics , linguistics , philosophy
Click reactions have the advantages of high reactivity, excellent orthogonality, and synthetic accessibility. Inspired by click reactions, we propose the concept of “clipped aptamers”, whose binding affinity is regulated by the “clip”‐like specific interaction between a synthetic DNA‐mismatch‐binding small molecule (molecular glue, Z ‐NCTS) and the preset CGG/CGG sequences in nucleic acid sequences. In this study, we investigated a Z ‐NCTS‐mediated de novo selection of clipped aptamers against epithelial cell adhesion molecule. The generated clipped aptamers can achieve the efficient transition from a binding‐inactive state to an active state by clipping of Z ‐NCTS with two CGG sites, which otherwise would not hybridize. The experimental and simulation results showed that the clipped aptamer had ideal binding thermodynamics and the ability to regulate cellular adhesion. Because of this superior activated mechanism and structural diversity, clipped aptamers hold great potential in biosensing, imaging, conditional gene‐ and cellular behavior‐regulation, and drug delivery.