Synthesis, screening and crystallization of small molecules targeting protein-protein interactions

本项目部分的目标是合成、筛选和优化适合于药物干扰蛋白质-蛋白质相互作用的小分子有机化合物。然后将具有生物活性的化合物与其目标蛋白结晶，以确定相应的蛋白质-配体复合体的结构。为此，提供了化学合成的和商业上可用的小分子化合物文库，开发了分析方法，并提供了高通量筛选的适当基础设施。本文提出的某些项目将需要设计和合成重点突出的库。适用于高通量筛选(HTS)的生物检测方法是与各个研究小组合作开发的。在二次分析和结晶筛选中进一步评估一次命中。三维结构将指导化合物的合成优化，这些化合物为äS改进了蛋白质功能研究的工具。

The aim of this project section is the synthesis, screening, and optimization of small organic compounds suitable for pharmacological interference with protein-protein interactions. Biologically active compounds will then be crystallized with their target proteins for structure determination of the corresponding protein-ligand complex. For this purpose, chemically synthesized and commercially available small-molecule compound libraries are provided, assay methodologies are developed, and the appropriate infrastructure for high-throughput screening is made available. Certain of the projects proposed herein will require the design and synthesis of focussed libraries. Bioassays suitable for high-throughput screening (HTS) are developed in collaboration with individual research groups. Primary hits are further evaluated in secondary assays and crystallization screens. Three-dimensional structures will guide the synthetic optimization of compounds that serve äs improved tools for the functional investigation of proteins.