State Key Laboratory of NBC Protection for Civilian, Beijing, 102205, China.
State Key Laboratory of NBC Protection for Civilian, Beijing, 102205, China.
Talanta. 2023 Jan 15;252:123840. doi: 10.1016/j.talanta.2022.123840. Epub 2022 Aug 18.
Currently, many aptamers of different target molecules have been screened by systematic evolution of ligands by exponential enrichment (SELEX) method. However, since the crystal structure of aptamers is complicated to obtain, few studies focus on the quantitative structure activity relationship (QSAR) of aptamers. It is significant to develop a virtual screening method for aptamers based on the QSAR model. In this study, a piezoresistive micro-cantilever aptasensor was fabricated to quantificationally detect ricin based on a new aptamer obtained via a virtual screening method. The advanced screening method based on the established QSAR model can screen aptamers formed by site-directed mutation of bases. The results of intermolecular interactions and molecular docking displayed that the new aptamer was mainly bound to ricin A-chain, and its combination of ricin with ricin B-chain aptamer has a significant synergistic effect. Due to the aptamer with excellent performance and the good linear relationship between the relative resistance change and the vertical deformation of the micro-cantilever, the piezoresistive micro-cantilever aptasensor emerged a linear detection range from 7.5 pg mL to 75 ng mL (R = 0.949) with the limit of detection 750 fg mL (S/N ≥ 3) for ricin. Furthermore, the proposed piezoresistive micro-cantilever sensor displayed excellent analytical performance with good reproducibility and high specificity.
目前，已有许多不同靶分子的适体通过指数富集配体系统进化（SELEX）方法被筛选出来。然而，由于适体的晶体结构难以获得，因此很少有研究关注适体的定量构效关系（QSAR）。基于 QSAR 模型开发适体的虚拟筛选方法具有重要意义。本研究基于一种新的通过虚拟筛选方法获得的适体，制备了压阻式微悬臂梁适体传感器，用于定量检测蓖麻毒素。基于建立的 QSAR 模型的先进筛选方法可以筛选出通过碱基定点突变形成的适体。分子间相互作用和分子对接的结果表明，新的适体主要与蓖麻毒素 A 链结合，其与蓖麻毒素 B 链适体的结合具有显著的协同作用。由于该适体具有优异的性能，且微悬臂梁的相对电阻变化与垂直变形之间具有良好的线性关系，因此压阻式微悬臂梁适体传感器对蓖麻毒素的线性检测范围为 7.5 pg mL 至 75 ng mL（R = 0.949），检测限为 750 fg mL（S/N ≥ 3）。此外，所提出的压阻式微悬臂梁传感器具有良好的重现性和高特异性，表现出优异的分析性能。
