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

靶向蛋白质-蛋白质相互作用的小分子的合成、筛选和结晶

• 批准号: 35757256
• 负责人: Professor Dr. Jörg Rademann
• 金额: --
• 依托单位: Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP)
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2012-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/35757256?language=en
• 关键词: Synthesis; screening; crystallization; small; molecules

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.

该项目部分的目的是合成、筛选和优化适合药理学干扰蛋白质-蛋白质相互作用的小有机化合物。然后，生物活性化合物将与其目标蛋白质一起结晶，以确定相应的蛋白质-配体复合物的结构。为此，提供了化学合成和市售的小分子化合物库，开发了测定方法，并提供了用于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库。适合高通量筛选 (HTS) 的生物测定是与各个研究小组合作开发的。在二次测定和结晶筛选中进一步评估初级命中。三维结构将指导化合物的合成优化，作为蛋白质功能研究的改进工具。