Identifying bioisosteres for cationic epigenetic motifs

鉴定阳离子表观遗传基序的生物等排体

• 批准号: 522177-2017
• 负责人: Hof, Fraser
• 金额: $ 1.82万
• 依托单位: University of Victoria
• 依托单位国家: 加拿大
• 项目类别: Engage Grants Program
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=640467
• 关键词: Identifying; bioisosteres; cationic; epigenetic; motifs

This project aims to identify a family of molecules that can generally bind to conserved binding pockets inepigenetic proteins. These molecules (called bioisosteres) would be generally useful starting points forepigenetic drug development efforts, as well as valuable tools for basic research into epigenetic modulators.ChemRoutes has a family of scaffold molecules - called ChemCores - that are potentially well suited to bind toepigenetic methyl reader pockets. The Hof lab at UVic are world leaders in the development of biochemicalassays for binding to such proteins. The proposal is first to establish a panel of fluorescence polarization assaysfor five distinct methyl reader proteins, and then to run three series of proprietary compounds prepared byChemRoutes through the panel of assays. The project will identify novel bioisosteres that ChemRoutes will beable to leverage in further research efforts and partnerships towards epigenetic modulation.

该项目旨在确定一个家族的分子，通常可以结合保守的结合口袋表观遗传蛋白。这些分子（称为生物电子等排体）通常是表观遗传药物开发工作的有用起点，也是表观遗传调节剂基础研究的宝贵工具。ChemRoutes有一个称为ChemCores的支架分子家族，可能非常适合结合表观遗传甲基阅读口袋。UVic的霍夫实验室在开发与这些蛋白质结合的生化分析方面处于世界领先地位。该建议首先建立一个针对五种不同甲基读取蛋白的荧光偏振分析小组，然后通过该分析小组运行ChemRoutes制备的三个系列的专有化合物。该项目将确定新的生物电子等排体，ChemRoutes将能够在进一步的研究工作和合作伙伴关系中利用这些生物电子等排体进行表观遗传调节。