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）：要求对配备低温探针和Tecan机器人的Bruker Avance III 700 MHz NMR光谱仪进行资金，用于全自动化合物库筛选，以支持研究人员财团的生物医学研究。基于NMR的筛选非常通用：适用于广泛的目标和复合文库以及配体结合亲和力。因此，它对药物发现并将新药物进步到诊所产生了重要影响。 NMR筛选补充了传统的高通量筛选技术，允许进行命中验证和优化（提供有关绑定方式的结构信息）。该请求的工具将立即对达特茅斯学院，达特茅斯医学院和诺里斯棉花癌中心以及包括佛蒙特大学医学院，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在内的区域大学以及包括佛蒙特大学医学院，包括佛蒙特大学医学院，包括诺里斯棉花癌中心的生物医学研究。项目包括抑制重要信号转导级联中关键蛋白质 - 蛋白质相互作用，筛查竞争性和变构酶抑制剂的筛查以及对天然产物合理修饰的结构见解。该乐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活科学中。该设施的额外支持包括NMR技术人员的薪水以及最近的两位研究科学家的招聘：一项具有超过8年的工业经验在图书馆筛选中利用NMR的工业经验，而第二次具有与合成化学方面的专业知识，以阐明命中率或夹带优化片段。借助这些专业知识，生物医学研究人员将很容易访问该设施，而筛查或NMR经验很少。对设施运营的监督将由三个主要用户的咨询委员会保证。已经成立了由NMR筛查领先专家的外部咨询委员会，以协助开发技术的最佳利用和应用。 公共卫生相关性：请求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，骨质疏松症和药物成瘾的铅候选者的重要数据。

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