Identifying bioisosteres for cationic epigenetic motifs

该项目旨在确定一个家族的分子，通常可以结合到保守的结合口袋的表观遗传蛋白。这些分子（称为生物同位体）通常是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有一个叫做ChemCores的支架分子家族，它们可能非常适合与表观遗传甲基读取器口袋结合。维多利亚大学的霍夫实验室在结合这类蛋白质的生化分析开发方面处于世界领先地位。该提案首先建立一个荧光偏振分析小组，用于五种不同的甲基解读蛋白，然后通过该小组分析运行chemroutes制备的三个系列专有化合物。该项目将确定新的生物同位体，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同位体进行表观遗传调节。

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.