Peptide Nucleic Acid (PNA)-Guided Peptide Engineering of an Aptamer Sensor for Protease-Triggered Molecular Imaging,Angewandte Chemie International Edition

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Peptide Nucleic Acid (PNA)-Guided Peptide Engineering of an Aptamer Sensor for Protease-Triggered Molecular Imaging
Angewandte Chemie International Edition ( IF 16.1 ) Pub Date : 2021-08-05 , DOI: 10.1002/anie.202106639
Zhichu Xiang ₁ , Jian Zhao ₁ , Deyu Yi ₁ , Zhenghan Di ₁ , Lele Li ₂

Affiliation

Protease-triggered control of functional DNA has remained unachieved, leaving a significant gap in activatable DNA biotechnology. Herein, we report the design of a protease-activatable aptamer system that can perform molecular sensing and imaging in a tumor-specific manner. The system is constructed by locking the structure-switching activity of an aptamer using a rationally designed PNA–peptide–PNA triblock copolymer. Highly selective protease-mediated cleavage of the peptide substrate results in reduced binding affinity of PNA to the aptamer module, with the subsequent recovery of its biosensing function. We demonstrated that the DNA/peptide/PNA hybrid system allows for tumor cell-selective ATP imaging in vitro and also produces a fluorescent signal in vivo with improved tumor specificity. This work illustrates the potential of bridging the gap between functional DNA and peptides for precise biomedical applications.

中文翻译：

用于蛋白酶触发分子成像的适体传感器的肽核酸 (PNA) 引导肽工程

蛋白酶触发的功能性 DNA 控制仍未实现，这在可激活的 DNA 生物技术中留下了重大空白。在此，我们报告了一种蛋白酶可激活适体系统的设计，该系统可以以肿瘤特异性方式进行分子传感和成像。该系统是通过使用合理设计的 PNA-肽-PNA 三嵌段共聚物锁定适体的结构转换活性来构建的。肽底物的高选择性蛋白酶介导裂解导致 PNA 与适体模块的结合亲和力降低，随后恢复其生物传感功能。我们证明了 DNA/肽/PNA 杂交系统允许在体外进行肿瘤细胞选择性 ATP 成像，并且还在体内产生具有改进的肿瘤特异性的荧光信号。

更新日期：2021-10-04

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