Identifying bioisosteres for cationic epigenetic motifs

该项目旨在识别一类分子，这些分子通常可以与表观遗传蛋白中保守的结合口袋结合。这些分子(称为生物等位基因)通常是色素遗传药物开发工作的有用起点，也是表观遗传调节器基础研究的宝贵工具。ChemRoutes有一系列支架分子-称为ChemCore-它们可能很适合结合到表观遗传甲基阅读器口袋上。UVic的霍夫实验室在开发与这些蛋白质结合的生化分析方法方面处于世界领先地位。该提议首先为五种不同的甲基阅读器蛋白质建立一个荧光偏振分析小组，然后通过该小组分析运行由ChemRoutes准备的三系列专利化合物。该项目将确定新的生物等位基因，ChemRoutes将能够在进一步的研究努力和合作伙伴关系中利用这些生物等位基因来实现表观遗传调节。

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.