Development of phosphorylation-inducing chimeric small molecules

磷酸化诱导嵌合小分子的开发

• 批准号: 10043054
• 负责人: Amit Choudhary
• 金额: $ 24万
• 依托单位: BROAD INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-19 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10043054
• 关键词: 5' -AMP-activated protein kinase; Adaptor Signaling Protein; Affinity; Agammaglobulinaemia tyrosine kinase; Attenuated; Binding; Biochemical; Biological; Breathing; Bromodomain; Cells; Chemicals; Complex; Computer Models; Dependence; Development; Dimerization; Dose; Enzymes; Equilibrium; Evaluation; Event; Exhibits; Exploratory/Developmental Grant; Future; HLA Antigens; Immune response; Immune system; Length; Ligands; Mediating; Membrane; Methods; Nature; Nuclear; Pharmaceutical Preparations; Phosphorylation; Phosphorylation Site; Phosphotransferases; Play; Protac; Protein Isoforms; Protein Kinase; Protein Kinase C; Protein Tyrosine Kinase; Protein-Serine-Threonine Kinases; Proteins; Proteomics; Research; Role; Serine/Threonine Phosphorylation; Signal Transduction; Specificity; Structure; Tacrolimus Binding Protein 1A; Therapeutic; Tyrosine Phosphorylation; computer studies; experimental study; immunoregulation; interest; loss of function; multidisciplinary; neoantigens; phosphoproteomics; programs; protein function; small molecule

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

项目概要 蛋白质磷酸化可以激活、抑制或改变蛋白质的功能。 通过激酶抑制进行磷酸化是存在的，但是可以根据需要诱导任何蛋白质磷酸化的方法 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)，通过剂量和时间控制诱导蛋白质磷酸化。 将通过将小分子激酶结合物与目标蛋白的小分子结合物连接而形成 活性激酶接近靶蛋白以启动磷酸化。 1