Acquisition of 700 MHz NMR for Automated Chemical/Peptide Library Screening

采集 700 MHz NMR 用于自动化学/肽库筛选

• 批准号: 7834726
• 负责人: DALE F MIERKE
• 金额: $ 183.33万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-15 至 2012-04-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7834726
• 关键词: Advisory Committees; Affinity; Binding; Biochemical; Biological Factors; Biological Sciences; Biomedical Research; Cancer Intervention; Chemicals; Clinic; Complement; Connecticut; Cystic Fibrosis; Data; Drug Addiction; Enzyme Inhibitor Drugs; Enzyme Inhibitors; Faculty; Funding Applicant; Health Sciences; Housing; Inflammation; Lead; Libraries; Ligand Binding; Massachusetts; Medicine; Modification; Molecular; Norris Cotton Cancer Center; Osteoporosis; Peptide Library; Research; Research Personnel; Robot; Scientist; Screening procedure; Signal Transduction; Synthesis Chemistry; Technology; Translating; Universities; Validation; Vermont; Wages; base; college; cryogenics; drug discovery; experience; high throughput screening; insight; instrument; medical schools; operation; protein protein interaction; public health relevance

DESCRIPTION (provided by applicant): Funding is requested for a Bruker Avance III 700 MHz NMR spectrometer equipped with a cryogenic probe and Tecan robot for fully automated compound library screening to support the biomedical research of a consortium of investigators. NMR-based screening is extremely versatile: applicable to a wide range of targets and compound libraries as well as ligand binding affinities. As such it has made an important impact on drug discovery and progressing new medicines into the clinic. NMR screening complements traditional high-throughput screening technologies allowing for hit validation and optimization (providing structural information on the mode of binding). The requested instrument will have an immediate impact on the biomedical research of the participating faculty from Dartmouth College, Dartmouth Medical School and the Norris Cotton Cancer Center and regional universities including University of Vermont Medical School, University of Massachusetts, University of Montreal, and University of Connecticut Health Science Center. Projects include inhibition of key protein-protein interactions in important signal transduction cascades, screening for competitive and allosteric enzyme inhibitors, and structural insight for rational modification of natural products. The instrument will form the basis of a screening facility to be housed in a new life sciences building under construction on the Dartmouth campus. Additional support of this facility includes that salary of an NMR technician as well as the recent recruitment of two research scientists: one with over 8 years of industrial experience in the utilization of NMR in library screening and a second with expertise in synthetic chemistry for elaboration of hits or tethering of optimized fragments. With this expertise available, the facility will be readily accessible to the biomedical researcher with little screening or NMR experience. Oversight of the facility operation will be guaranteed by an advisory committee of three of the primary users. An external advisory committee of leading experts in NMR screening has been formed to assist in optimal utilization of the facility and application of developing technologies. PUBLIC HEALTH RELEVANCE: The requested instrument and screening facility will provide vital data to translate fundamental biochemical discoveries into lead candidates for molecular intervention for cancer, cystic fibrosis, inflammation, osteoporosis, and drug addiction.

描述（由申请人提供）：请求资助配备低温探针和 Tecan 机器人的 Bruker Avance III 700 MHz NMR 波谱仪，用于全自动化合物库筛选，以支持研究人员联盟的生物医学研究。基于 NMR 的筛选用途极其广泛：适用于各种靶标和化合物库以及配体结合亲和力。因此，它对药物发现和新药进入临床产生了重要影响。 NMR 筛选补充了传统的高通量筛选技术，可实现命中验证和优化（提供有关结合模式的结构信息）。所要求的仪器将对达特茅斯学院、达特茅斯医学院和诺里斯·科顿癌症中心以及佛蒙特大学医学院、马萨诸塞大学、蒙特利尔大学和康涅狄格大学健康科学中心等地区大学参与教师的生物医学研究产生直接影响。项目包括抑制重要信号转导级联中的关键蛋白质-蛋白质相互作用、筛选竞争性和变构酶抑制剂以及对天然产物进行合理修饰的结构洞察。该仪器将构成筛查设施的基础，该设施将安置在达特茅斯校园正在建设的新生命科学大楼中。该设施的额外支持包括 NMR 技术人员的薪水以及最近招募的两名研究科学家：其中一名在利用 NMR 进行文库筛选方面拥有超过 8 年的行业经验，另一名则拥有合成化学方面的专业知识，可用于阐述命中或束缚优化片段。有了这些专业知识，几乎没有筛选或核磁共振经验的生物医学研究人员就可以轻松使用该设施。由三个主要用户组成的咨询委员会将保证对设施运营的监督。已成立由 NMR 筛选领域的顶尖专家组成的外部咨询委员会，以协助优化设施的利用和开发技术的应用。 公共卫生相关性：所需的仪器和筛查设施将提供 将基本生化发现转化为癌症、囊性纤维化、炎症、骨质疏松症和毒瘾分子干预的主要候选者的重要数据。

项目成果

Reining in polyoma virus associated nephropathy: design and characterization of a template mimicking BK viral coat protein cellular binding.

控制多瘤病毒相关肾病：模拟 BK 病毒外壳蛋白细胞结合的模板的设计和表征。

• DOI: 10.1021/bi300639d
• 发表时间: 2012
• 期刊: Biochemistry
• 影响因子: 2.9
• 作者: Audu,ChristopherO;O'Hara,Bethany;Pellegrini,Maria;Wang,Lei;Atwood,WalterJ;Mierke,DaleF
• 通讯作者: Mierke,DaleF