Bispecific Aptamer Induced Artificial Protein-Pairing: A Strategy for Selective Inhibition of Receptor Function

Journal of the American Chemical Society
Liping WangHuang-Hao Yang

Abstract

Cell surface receptors play a critical role in modulating intracellular signal transduction, making them important drug targets. However, it remains challenging to develop a selective and efficient strategy for regulating receptor function. Herein, we develop a strategy, called bispecific aptamer induced artificial protein-pairing, to selectively regulate receptor function. In this strategy, bispecific aptamer probes act as molecular mediators to bind to both a target receptor protein and a paired protein, which brings the two proteins into close proximity on the living cell membrane. Importantly, the paired proteins work not only as a cancer biomarker for enhancing cell selectivity but also as a blocking assistant to inhibit target receptor function via strong steric hindrance effect. Compared with single-aptamer-mediated regulation, the proposed bispecific aptamer probes afford substantial improvement in selective and efficient regulation of receptor function and downstream signaling pathways. This work offers a versatile methodology to design molecular mediators that can modulate receptor function, thereby providing a new way for developing novel therapeutic drugs.

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Citations

Feb 11, 2020·Chemical Society Reviews·Jingying LiHuanghao Yang
Jul 15, 2020·Pharmaceutics·Prabir Kumar KulabhusanMeral Yüce
Feb 11, 2021·Journal of the American Chemical Society·Emma E WatsonNicolas Winssinger
Apr 21, 2021·Chemical Communications : Chem Comm·Xiangnan WangJian-Hui Jiang
May 5, 2021·Journal of the American Chemical Society·Jinqi DengWeihong Tan
May 13, 2021·Chemical Communications : Chem Comm·Yu-Peng ZhangDai-Wen Pang
Jun 19, 2021·Angewandte Chemie·Momoko AkiyamaShinsuke Sando
Oct 29, 2019·Journal of the American Chemical Society·Wei ZhouXiaohong Fang
Dec 5, 2019·Journal of the American Chemical Society·Ying XiongYi Lu
Oct 28, 2019·Analytical Chemistry·Erin Marie McConnellYingfu Li
Jun 10, 2020·Journal of the American Chemical Society·Kaiming ChenWeihong Tan
Sep 9, 2021·Biomaterials Science·Qunye HeZhenbao Liu
Oct 5, 2021·Chemical Society Reviews·Lanlan ChenHuanghao Yang
Sep 23, 2021·Chembiochem : a European Journal of Chemical Biology·Masanobu NaganoKeitaro Yoshimoto

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