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

被引：13

作者：

Huang, Mengjiao ^{[1
]}

Li, Tingyu ^{[1
]}

Xu, Yuanfeng ^{[1
]}

Wei, Xinyu ^{[1
]}

Song, Jia ^{[2
]}

Lin, Bingqian ^{[1
]}

Zhu, Zhi ^{[1
]}

Song, Yanling ^{[1
]}

Yang, Chaoyong ^{[1
,2
]}

机构：

[1] Xiamen Univ, State Key Lab Phys Chem Solid Surfaces, MOE Key Lab Spectrochem Anal & Instrumentat, Key Lab Chem Biol Fujian Prov,Dept Chem Biol,Coll, Xiamen 361005, Fujian, Peoples R China

[2] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Inst Mol Med, Shanghai 200127, Peoples R China

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2021年 / 60卷 / 11期

基金：

中国国家自然科学基金;

关键词：

aptamers; gain of function; nucleic acids; regulation of binding affinity; selection; CLICK CHEMISTRY; DNA;

D O I：

10.1002/anie.202013570

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页码：6021 / 6028

页数：8

共 30 条

[1] EpCAM (CD326) finding its role in cancer (vol 96, pg 417, 2007) [J].