Nat Protoc：南京大學劉震教授研究團發表分子印跡研究論文

2017年4月6日， 國際學術權威刊物自然出版集團旗下子刊《Nature Protocols》線上發表了南京大學化學化工學院劉震教授研究團隊關於分子印跡領域的重要論文， 研究論文題為“Preparation of molecularly imprinted polymers specific to glycoproteins, glycans and monosaccharides via boronate affinity controllable-oriented surface imprinting”。 論文的共同第一作者為博士生邢榮榮和博士後王雙壽。

分子印跡是製備具有類似抗體或酶專一性仿生識別材料的重要技術， 在生物傳感、親和分離和疾病診斷等領域具有廣闊的應用前景。 但是， 蛋白質等生物分子的普適、高效印跡是分子印跡中的一個重要的挑戰， 傳統方法難以同時滿足不同大小的生物分子的印跡， 更難以對印跡過程進行精確控制。

經過多年在硼親和材料領域中的深入研究， 該研究團隊發展出硼親和可控定向表面印跡法。 該方法能夠便捷高效地製備出糖蛋白、聚糖和單糖的分子印跡聚合物。 該方法的原理見圖1， 先將範本分子固定到硼酸功能化的基質上， 然後利用生物相容性良好的功能單體在基質表面聚合， 形成合適厚度的印跡層以及與範本分子空間匹配的印跡腔。 該方法的最大優勢在於印跡可控性：根據範本分子尺寸大小， 調整印跡層厚度， 製備出不同尺寸範本的分子印跡聚合物， 而印跡層厚度只需要調節印跡時間來精確控制。 這不僅簡化了印跡步驟， 而且適用範圍廣。 所得分子印跡聚合物已經在疾病診斷、癌細胞靶向識別和活體單細胞分析等重要應用領域中展現出優越的分子識別性能。

圖1. 硼親和可控定向表面印跡原理

原文連結：

原文摘要：

Molecularly imprinted polymers (MIPs) are materials that are designed to be receptors for a template molecule (e.g., a protein). They are made by polymerizing the polymerizable reagents in the presence of the template; when the template is removed, the material can be used for many applications that would traditionally use antibodies. Thus, MIPs are biomimetic of antibodies and in this capacity have found wide applications, such as sensing, separation and diagnosis. However, many imprinting approaches are uncontrollable, and facile imprinting approaches widely applicable to a large variety of templates remain limited. We developed an approach called boronate affinity controllable–oriented surface imprinting, which allows for easy and efficient preparation of MIPs specific to glycoproteins, glycans and monosaccharides. This approach relies on immobilization of a template (glycoprotein, glycan or monosaccharide) on a boronic-acid-functionalized substrate through boronate affinity interaction, followed by self-polymerization of biocompatible monomer(s) to form an imprinting layer on the substrate with appropriate thickness. Imprinting in this approach is performed in a controllable manner, permitting the thickness of the imprinting layer to be fine-tuned according to the molecular size of the template by adjusting the imprinting time. This not only simplifies the imprinting procedure but also makes the approach widely applicable to a large range of sugar-containing biomolecules. MIPs prepared by this approach exhibit excellent binding properties and can be applied to complex real samples. The MIPs prepared by this protocol have been used in affinity separation, disease diagnosis and bioimaging. The entire protocol, including preparation, property characterization and performance evaluation, takes ~3–8 d, depending on the type of substrate and template used.