Discovery of Chemical Probes and Therapeutic Leads: Cryoprobe Upgrade of a 400 MHz NMR

项目摘要 这个生物医学研究卓越中心的目标是继续努力开发分子 探索生物学途径，发现和应用生物学研究的新化学生物学工具 与疾病相关的途径，并开发计算机方法来理解小分子 分子与复杂大分子靶标的相互作用。在合成、生物化学、 工程和生物学，我们的科学团队将开发新的化学生物学工具来理解 细菌病原体在宿主细胞内生存和复制的细胞和分子机制，新的 用化学工具和核苷酸类似物了解a‘甲基对mRNA去甲基化的调节 橡皮擦酶及其在人类癌症中的失调，分子定义的纳米颗粒佐剂产生 肺部的特异性免疫反应，以促进可吸入疫苗的开发，并计算 小分子调控病毒结构和功能机制的研究进展 冰盖。 Cobre的资金将用于招聘两名新的教职员工，他们将补充现有的 我们的中心，将通过竞争性试点赠款进行扩展。在科布雷的第四年和第五年，五二- 将为年度更换项目提供资金。特拉华州和全国的协作和资源共享 IDEA网络对于最大化我们的研究能力、核心设施和指导网络将是至关重要的。在……里面 第二阶段，科布雷继续开发独特的核心设施，促进高通量合成， 化学探针的提纯、筛选和分析。在第一阶段建立的基础设施的基础上， 我们将支持分析化学领域的一个核心设施，它将为#年的关键核心设施提供支持 质谱学、溶液核磁共振和动力学分析。该中心还将支持合成和发现 核心设施，将为小型企业提供定制的合成服务以及仪器和基础设施 分子合成、高通量催化剂发现、并行合成、计算和显微镜。

Project Summary The goal of this Center of Biomedical Research Excellence is to continue our efforts to develop molecular approaches for probing biology, to discover and apply new chemical biology tools for the study of biological pathways associated with disease, and to develop computational approaches for understanding small molecule interactions with complex macromolecular targets. With core strengths in synthesis, biochemistry, engineering and biology, our scientific team will develop new chemical biology tools for understanding the cellular and molecular mechanisms that bacterial pathogens use to survive and replicate inside host cells, new chemical tools and nucleotide analogs to understand the regulation of mRNA demethylation by a ‘methyl eraser’ enzyme and its dysregulation in human cancer, molecularly-defined nanoparticle adjuvants that yield specific immune responses in the lung to advance inhalable vaccine development, and computational approaches to elucidate the mechanisms by which small molecules regulate the structure and function of virus capsids. COBRE funding will be used to recruit two new faculty members who will complement the existing strengths of our center, which will be expanded through competitive pilot grants. In years 4 and 5 of the COBRE, five two- year replacement projects will be funded. Collaboration and resource sharing in the Delaware and national IDeA network will be critical for maximizing our research capacity, core facilities and mentoring network. In Phase II, this COBRE continue to develop unique core facilities that facilitates high throughput synthesis, purification, screening and analysis of chemical probes. Building on the infrastructure established in Phase I, we will support a core facility in Analytical Chemistry, which will provide support for critical core facilities in mass spectrometry, solution NMR and kinetic analysis. The center will also support a Synthesis and Discovery core facility, which will provide custom synthesis services and instrumentation and infrastructure for small molecule synthesis, high throughput catalyst discovery, parallel synthesis, computation and microscopy.