State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210023, China.
Acc Chem Res. 2017 Sep 19;50(9):2185-2193. doi: 10.1021/acs.accounts.7b00179. Epub 2017 Aug 29.
Due to the complexity of biological systems and samples, specific capture and targeting of certain biomolecules is critical in much biological research and many applications. cis-Diol-containing biomolecules, a large family of important compounds including glycoproteins, saccharides, nucleosides, nucleotides, and so on, play essential roles in biological systems. As boronic acids can reversibly bind with cis-diols, boronate affinity materials (BAMs) have gained increasing attention in recent years. However, real-world applications of BAMs are often severely hampered by three bottleneck issues, including nonbiocompatible binding pH, weak affinity, and difficulty in selectivity manipulation. Therefore, solutions to these issues and knowledge about the factors that influence the binding properties are of significant importance. These issues have been well solved by our group in past years. Our solutions started from the synthesis and screening of boronic acid ligands with chemical moieties favorable for binding at neutral and acidic pH. To avoid tedious synthesis routes, we proposed a straightforward strategy called teamed boronate affinity, which permitted facile preparation of BAMs with strong binding at neutral pH. To enhance the affinity, we confirmed that multivalent binding could significantly enhance the affinity toward glycoproteins. More interestingly, we observed that molecular interactions could be significantly enhanced by confinement within nanoscale spaces. To improve the selectivity, we investigated interactions that govern the selectivity and their interplays. We then proposed a set of strategies for selectivity manipulation, which proved to be useful guidelines for not only the design of new BAMs but also the selection of binding conditions. Applications in metabolomic analysis, glycoproteomic analysis, and aptamer selection well demonstrated the great potential of the prepared BAMs. Molecular imprinting is an important methodology for creating affinity materials with antibody-like binding properties. Boronate affinity-based covalent imprinting is a pioneering approach in molecular imprinting, but only a few cases of successful imprinting of glycoproteins by this method were reported. With sound understanding of boronate affinity, we developed two facile and generally applicable boronate affinity-based molecular imprinting approaches. The resulting boronate affinity molecularly imprinted polymers (MIPs) exhibited dramatically improved binding properties, including biocompatible binding pH range, enhanced affinity, improved specificity, and superb tolerance to interference. In terms of nanoconfinement effect, we explained why the binding pH range was widened and why the affinity was enhanced. The excellent binding properties made boronate affinity MIPs appealing alternatives to antibodies in promising applications such as disease diagnosis, cancer-cell targeting, and single-cell analysis. In this Account, we survey the key aspects of BAMs, the efforts we made to solve these issues, and the connections between imprinted and nonimprinted BAMs. Through this survey, we wish to pave a sound fundamental basis of the dependence of binding properties of BAMs on the nature and structure of the ligands and the supporting materials, which can facilitate the development and applications of BAMs. We also briefly sketch remaining challenges and directions for future development.
由于生物系统和样本的复杂性，特定的生物分子捕获和靶向在许多生物研究和应用中至关重要。顺二醇基生物分子是一类重要的化合物，包括糖蛋白、糖、核苷、核苷酸等，在生物系统中发挥着重要作用。由于硼酸可以与顺二醇基可逆结合，硼酸盐亲和材料（BAMs）近年来受到越来越多的关注。然而，BAMs 的实际应用常常受到三个瓶颈问题的严重阻碍，包括非生物相容性的结合 pH 值、弱亲和力和选择性操作的困难。因此，解决这些问题以及影响结合特性的因素的知识具有重要意义。这些问题在过去几年中已被我们小组很好地解决。我们的解决方案始于具有化学基团的硼酸配体的合成和筛选，这些化学基团有利于在中性和酸性 pH 值下结合。为了避免繁琐的合成路线，我们提出了一种称为联合硼酸盐亲和性的简单策略，该策略允许在中性 pH 值下轻松制备具有强结合能力的 BAMs。为了增强亲和力，我们证实了多价结合可以显著增强对糖蛋白的亲和力。更有趣的是，我们观察到分子相互作用可以通过限制在纳米尺度空间中得到显著增强。为了提高选择性，我们研究了控制选择性的相互作用及其相互作用。然后，我们提出了一套用于选择性操作的策略，这些策略不仅对新型 BAMs 的设计，而且对结合条件的选择都提供了有用的指导。代谢组学分析、糖蛋白质组学分析和适体选择的应用很好地证明了所制备的 BAMs 的巨大潜力。分子印迹是一种用于创建具有抗体样结合特性的亲和材料的重要方法。基于硼酸盐亲和性的共价印迹是分子印迹的一种开创性方法，但只有少数成功报道了该方法对糖蛋白的印迹。基于对硼酸盐亲和性的深入了解，我们开发了两种简单且通用的基于硼酸盐亲和性的分子印迹方法。所得的硼酸盐亲和性分子印迹聚合物（MIPs）表现出显著改善的结合性能，包括生物相容性的结合 pH 值范围、增强的亲和力、提高的特异性和对干扰的超强耐受性。在纳米限域效应方面，我们解释了为什么结合 pH 值范围变宽以及为什么亲和力增强。良好的结合性能使硼酸盐亲和性 MIPs 在疾病诊断、癌细胞靶向和单细胞分析等有前途的应用中成为抗体的有吸引力的替代品。在本综述中，我们调查了 BAMs 的关键方面、我们为解决这些问题所做的努力以及印迹和非印迹 BAMs 之间的联系。通过这一综述，我们希望为 BAMs 的结合性能对配体和支撑材料的性质和结构的依赖奠定坚实的基础，从而促进 BAMs 的发展和应用。我们还简要概述了剩余的挑战和未来的发展方向。
