The use of aptamers in bioanalytical and biomedical applications exploits their ability to recognize cell surface protein receptors. Targeted therapeutics and theranostics come to mind in this regard. However, protein receptors occur on both cancer and normal cells; as such, aptamers are now taxed with identifying high vs. low levels of protein expression. Inspired by the flexible template mechanism and elegant control of natural nucleic acid-based structures, we report an allosteric regulation strategy for constructing a structure-switching aptamer for enhanced target cell recognition by engineering aptamers with DNA intercalated motifs (i-motifs) responsive to the microenvironment, such as pH. Structure-switching sensitivity can be readily tuned by manipulating i-motif sequences. However, structure-switching sensitivity is difficult to estimate, making it equally difficult to effectively screen modified aptamers with the desired sensitivity. To address this problem, we selected a fluorescent probe capable of detecting G-quadruplex in complicated biological media.

中文翻译：

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工程化 G-四联适体以调节其结合特异性


适体在生物分析和生物医学应用中的使用利用了它们识别细胞表面蛋白受体的能力。在这方面，我们想到了靶向治疗和治疗诊断学。然而，蛋白质受体同时存在于癌细胞和正常细胞上。因此，适配体现在需要识别高和低的值。蛋白质表达水平低。受灵活的模板机制和对天然核酸结构的优雅控制的启发，我们报告了一种变构调节策略，用于构建结构转换适体，通过对具有 DNA 插入基序（i-motifs）的工程适体进行响应来增强靶细胞识别。微环境，例如pH值。通过操纵 i-motif 序列可以轻松调节结构转换灵敏度。然而，结构转换的灵敏度很难估计，这使得有效筛选具有所需灵敏度的修饰适体同样困难。为了解决这个问题，我们选择了一种能够在复杂的生物介质中检测 G-四链体的荧光探针。