Activation of Aptamers with Gain of Function by Small‐Molecule‐Clipping of Intramolecular Motifs. Issue 11 (27th January 2021)

• Record Type: Journal Article
• Authors: Huang, Mengjiao; Li, Tingyu; Xu, Yuanfeng; Wei, Xinyu; Song, Jia; Lin, Bingqian; Zhu, Zhi; Song, Yanling; Yang, Chaoyong
• Is Part Of: Angewandte Chemie international edition. Volume 60:Issue 11(2021)
• Page Start: 6021
• Page End: 6028
• Publication Date: 2021-01-27
• Subjects: aptamers -- gain of function -- nucleic acids -- regulation of binding affinity -- selection; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202013570
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: 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. Abstract : A small‐molecule‐mediated selection method was developed to obtain a "clipped aptamer" with activatable binding affinity toward its target. The aptamer's binding can be activated by "clipping" two intramolecular motifs via a synthetic DNA‐mismatch‐binding small molecule.