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Activation of Aptamers with Gain of Function by Small-Molecule-Clipping of Intramolecular Motifs.

Mengjiao HuangTingyu LiYuanfeng XuXinyu WeiJia SongBingqian LinZhi ZhuYanLing SongChaoyong James Yang
Published in: Angewandte Chemie (International ed. in English) (2021)
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.
Keyphrases
  • nucleic acid
  • small molecule
  • cell adhesion
  • drug delivery
  • binding protein
  • protein protein
  • gold nanoparticles
  • escherichia coli
  • high resolution
  • genome wide
  • atomic force microscopy
  • label free