Development of artificial receptors that can recognize a specific protein surface in aqueous solution

在项目期间，对磷酸化蛋白质和多肽的分子识别化学在基础科学和应用方面都有了很大的进步。我的团队新开发了基于锌金属络合物的人造受体分子，这种分子可以识别磷酸化的多肽和蛋白质，并通过荧光信号的变化来感知它们。这些都可以在水溶液和SDS-PAGE凝胶板中进行。等温滴定量热法的详细研究表明，受体的锌中心与多肽的阴离子磷酸中心紧密结合，从而显示出很强的亲和力。此外，利用这种强结合，我们还测试了受体对磷酸化蛋白相互作用的抑制能力。在双核锌复合型受体的交联结合模式下，很明显，有效地破坏了聚合酶的WW结构域和磷酸化的C-末端结构域之间的磷酸化蛋白相互作用。这些结果清楚地表明，人工受体不仅可以作为磷酸化多肽和蛋白质的简单荧光化学传感器，还可以作为磷酸化蛋白质相互作用的潜在干扰物。预计目前的研究成果将有力地促进相关研究，并可能在不久的将来导致更复杂的分子。

During the project term, molecular recognition chemistry toward phosphorylated proteins and peptides has greatly advanced both in fundamental science and application. My group newly developed artificial receptor molecules based on Zn-metal complexes which can recognize phosphorylated peptides and proteins and sense them by a fluorescence signal change. These can be carried out in aqueous solution and SDS-PAGE gel plates. Detailed study using isothermal titration calorimetry clearly demonstrates that the Zn sites of the receptors tightly bind to the anionic phospate sites of the peptide and thus shows the strong affinity. Further more, using this strong binding, we also tested the inhibition capability of the receptors for the phospho-protein protein interactions. In the case of the cross-linking binding mode of the dinuclear Zn complex type of receptors, it is clear that the effective disruption of the phospho-protein protein interactions between WW domain and the phosphorylated C-terminal domain of Polymerase. These results clearly indicate that artificial receptors can act not only as a simple fluorescent chemosensor for phosphorylated peptides and proteins, but also as a poteintial disruptor for the phospho-protein protein interactions. It is expected that the present accomplishment strongly stimulate the relevant research and may lead to a more sophisticated molecule in the near future.