Development of phosphorylation-inducing chimeric small molecules

项目总结 蛋白质磷酸化可以激活、抑制或修饰蛋白质的功能。阻止蛋白质的小分子 存在通过抑制激酶的磷酸化，但根据需要诱导任何蛋白质的磷酸化的方法 都不存在。我们建议开发一类新的小分子，称为磷酸化诱导嵌合体 小分子(PHICS)，将诱导蛋白质磷酸化，并具有剂量和时间控制。PHICS 将目标蛋白的小分子结合蛋白与小分子蛋白结合形成 活性激酶被带到目标蛋白附近以启动磷酸化。 1

PROJECT SUMMARY Protein phosphorylation can activate, inhibit, or modify protein’s function. Small molecules that block protein phosphorylation via kinase inhibition exist, but methods to induce phosphorylation of any protein on demand do not exist. We propose to develop a new class of small molecules, termed PHosphorylation Inducing Chimeric Small molecules (PHICS), which will induce protein phosphorylation with dose and temporal control. PHICS will be formed by joining a small-molecule kinase binder with a small-molecule binder of the target protein so that an active kinase is brought into proximity to the target protein to initiate phosphorylation. 1