论文标题 / Synthesis and Applications of Boronate Affinity Materials: From Class Selectivity to Biomimetic Specificity
期刊 / Accounts of Chemical Research
发表时间 / 2017-08-29
数字识别码 / 10.1021/acs.accounts.7b00179
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.
近日，美国化学会旗下刊物《化学研究评述》（Accounts of Chemical Research）在线发表了我校刘震教授研究团队撰写的题目为“Synthesis and Applications of Boronate Affinity Materials: From Class Selectivity to Biomimetic Specificity”的特邀综述性论文（Acc. Chem. Res., DOI: 10.1021/acs.accounts.7b00179）。论文系统地介绍了该课题组在硼亲和材料领域的研究工作。
硼亲和材料在近十来年取得了显著进步，我校刘震教授课题组在该领域做出了系统和深入的研究。该团队针对常规硼亲和材料存在的局限，从硼亲和配基的合成与筛选入手，在此基础上阐明了硼亲和作用相关的分子间相互作用机制和结构-性能关系，提出了增强亲和力和选择性的策略，先后发展出一系列性能先进的硼亲和材料，克服了常规硼亲和材料难以胜任生理pH条件和复杂样品体系中的低浓度目标物的识别的局限，所得的硼亲和材料在亲和分离、组学研究和适配体筛选等领域获得了成功的应用。将硼亲和相互作用与分子印迹技术相结合，该团队进一步发展出多个便捷、通用、高效的分子印迹方法，制备出系列分子识别性能优异的硼亲和印迹材料；尤其是硼亲和可控定向表面印迹法，可以利用模板的分子尺寸预测最佳的印迹时间，且免疫原性差、抗体难以制备的聚糖等目标分子，利用该技术可以便捷地制备得到相应的分子印迹聚合物，将分子印迹技术推向一个全新的高度。该团队发展出的分子印迹技术可以和量子点、介孔纳米材料和等离激元材料等各种先进材料相结合，得到先进功能的仿生识别材料。这些仿生识别材料已经作为抗体的替代物在疾病诊断、翻译后修饰蛋白质鉴定、癌细胞靶向识别和单细胞分析等领域获得了重要应用。相关研究工作已在德国《应用化学》（Angew. Chem. Int. Ed., 2009, 48, 6704-6707; 2013, 52, 7451-7454; 2014, 53, 10386-10389; 2015, 54, 6173-6176; 2015, 54, 10211-10215 (VIP)；2016, 55, 13215-13218）、英国《化学科学》（Chem. Sci., 2012, 3, 1467-1471; 2013, 4, 4298-4303; 2014, 5, 1135-1140; 2014, 5, 4065-4069）和《自然-实验指南》（Nat. Protoc., 2017, 12, 964–987）等重要期刊上发表系列高水平研究论文55篇，已申请发明专利16项，获授权发明专利10项。这些研究成果产生了重要影响，Chemistry World和LCGC 等杂志专题介绍了相关工作，获John Wiley、Royal Society of Chemistry和Humanna等出版社的邀请，已出版专章4章，发表高水平综述论文1篇（Chem. Soc. Rev., 2015, 44, 8097-8123）。由于以上贡献，刘震教授被选为国际分子印迹学会理事和分析化学领域核心期刊Anal. Chim. Acta杂志编委。