Protein and Small Molecule Chemistry

项目摘要/摘要：核心C 蛋白质和小分子化学核心的作用是所有研究人员需要的中心 计划项目建议书。核心将为项目调查人员提供获得纯化蛋白质和类似病毒的途径 粒子(VLP)以及小分子和多肽的定制合成。核心还将构建 根据研究人员的需要，通过定点突变获得蛋白质的突变版本。最后，核心将 描述和量化蛋白质-蛋白质和蛋白质-配体的相互作用。核心活动的示例包括 诺如病毒蛋白水解酶的纯化及其药物发现和VLP的纯化 抗体与衣壳的相互作用。活性还包括合成小分子蛋白酶抑制剂。 生物化学和基于细胞的测试以及结构研究的候选人。此外，核心将 测定小分子与诺如病毒蛋白酶的结合亲和力以及抗体-VLP的亲和力 项目研究人员所需的相互作用和其他蛋白质-蛋白质相互作用。最后，核心将 构建诺如病毒蛋白水解酶、p22和p41基因以及其他所需的定点突变 由项目调查人员进行的功能研究。核心人员在方法方面有丰富的经验 提供这些服务所需的所有设备和资源均可在 核心。诸如蛋白质提纯和小分子合成、诱变、 而核心设施中的约束性测量避免了个别调查人员获得 它是促进在实现科学目标方面取得进展的一种有效手段 这个项目。

PROJECT SUMMARY/ABSTRACT: Core C The role of the Protein and Small Molecule Chemistry Core is central to the needs of all the investigators in the Program Project Proposal. The Core will provide project investigators access to purified proteins and virus-like particle (VLPs) as well as custom synthesis of small molecules and peptides. The Core will also construct mutant versions of proteins by site-directed mutagenesis as needed by investigators. Finally, the Core will characterize and quantitate protein-protein and protein-ligand interactions. Examples of Core activities include purification of norovirus protease to facilitate drug discovery and purification of VLPs for investigations of antibody interactions with capsid. Activities also include synthesis of small molecule protease inhibitor candidates for biochemical and cell-based testing as well as structural studies. In addition, the Core will measure binding affinity of small molecules with norovirus protease as well as affinity of antibody-VLP interactions and other protein-protein interactions as needed by project investigators. Finally, the Core will construct site-directed mutations in the norovirus protease, p22, and p41 genes and others as needed for functional studies by project investigators. The Core personnel have extensive experience in the methods required for providing these services and all of the equipment and resources necessary are available in the Core. The performance of services such as protein purification and small molecule synthesis, mutagenesis, and binding measurements in a Core facility avoids the need for individual investigators to acquire the necessary expertise and equipment and is an efficient means of facilitating progress on the scientific goals of the project.