Molecular Crowding Evolution for Enabling Discovery of Enthalpy-Driven Aptamers for Robust Biomedical Applications.,Analytical Chemistry

当前位置： X-MOL 学术 › Anal. Chem. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Molecular Crowding Evolution for Enabling Discovery of Enthalpy-Driven Aptamers for Robust Biomedical Applications.
Analytical Chemistry ( IF 6.7 ) Pub Date : 2019-07-26 00:00:00 , DOI: 10.1021/acs.analchem.9b02697
Mengjiao Huang ₁ , Jia Song ₂ , Peifeng Huang ₁ , Xiaofeng Chen ₁ , Wei Wang ₂ , Zhi Zhu ₁ , Yanling Song _{1,

2} , Chaoyong Yang _{1,

2}

Affiliation

An enthalpy-driven ligand is an ideal probe for practical applications because of the formation of abundant specific bonds between the ligand and target, compared to an entropy-driven ligand with a similar Gibbs free energy change. However, there has been a lack of direct discovery strategy for identifying enthalpy-driven ligands. In this work, a molecular crowding SELEX (systematic evolution of ligands by exponential enrichment) strategy for discovering enthalpy-driven aptamers was developed to improve the affinity and selectivity of aptamers in complex samples. Three aptamer sequences were successfully evolved against a tumor biomarker protein, and all proved to be enthalpy-driven by thermodynamics analysis, establishing the feasibility of molecular crowding SELEX for effective discovery of enthalpy-driven aptamers. Further comparison of aptamers evolved from conventional SELEX in buffer and molecular crowding SELEX (SYL-H2C) revealed much higher affinity of SYL-H2C. With its improved thermodynamic properties, the enthalpy-driven SYL-H2C aptamer was able to detect circulating tumor cells in real cancer patient blood samples with excellent detection accuracy (10/10). The proposed molecular crowding screening strategy offers a promising direction for discovering robust binding probes for a great variety of biomedical applications.

中文翻译：

分子拥挤进化，以发现用于健壮生物医学应用的焓驱动适体。

与具有相似吉布斯自由能变化的熵驱动配体相比，焓驱动配体是在实际应用中的理想探针，因为在配体和靶标之间形成了丰富的特异性键。然而，一直缺乏直接发现策略来鉴定焓驱动的配体。在这项工作中，开发了一种分子拥挤的SELEX（通过指数富集的配体系统进化）策略来发现焓驱动的适体，以提高复杂样品中适体的亲和力和选择性。成功地针对肿瘤生物标志物蛋白进化出了三个适体序列，并且通过热力学分析证明它们均是焓驱动的，从而建立了分子拥挤SELEX用于有效发现焓驱动的适体的可行性。在缓冲液和分子拥挤SELEX（SYL-H2C）中从常规SELEX进化而来的适体的进一步比较表明，SYL-H2C具有更高的亲和力。焓驱动的SYL-H2C适体具有改进的热力学性质，能够以优异的检测精度检测真实癌症患者血液样本中的循环肿瘤细胞（10/10）。提出的分子拥挤筛选策略为发现适用于多种生物医学应用的坚固结合探针提供了一个有希望的方向。

更新日期：2019-07-26

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南