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）：申请资助配备低温探针和Tecan机器人的Bruker Avance III 700 MHz NMR光谱仪，用于全自动化合物库筛选，以支持研究者联盟的生物医学研究。基于NMR的筛选是非常通用的：适用于广泛的目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，允许命中验证和优化（提供关于结合模式的结构信息）。所要求的仪器将对来自达特茅斯学院、达特茅斯医学院和诺里斯棉花癌症中心以及包括佛蒙特大学医学院、马萨诸塞州大学、蒙特利尔大学和康涅狄格大学健康科学中心在内的地区大学的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，以及对天然产物合理修饰的结构洞察。该仪器将构成一个筛选设施的基础，该设施将设在达特茅斯校园正在建设的一座新的生命科学大楼内。该设施的其他支持包括一名核磁共振技术员的工资以及最近招募的两名研究科学家：一名在利用核磁共振进行文库筛选方面具有8年以上的工业经验，另一名具有合成化学方面的专门知识，用于精心制作命中或优化片段的束缚。有了这种专门知识，该设施将很容易访问的生物医学研究人员几乎没有筛选或核磁共振经验。由三个主要用户组成的咨询委员会将保证对设施运作的监督。已经成立了一个由核磁共振筛选方面的主要专家组成的外部咨询委员会，以协助最佳利用该设施和应用正在开发的技术。 公共卫生相关性：所要求的仪器和筛查设施将提供 重要的数据，将基本的生物化学发现转化为癌症，囊性纤维化，炎症，骨质疏松症和药物成瘾的分子干预的主要候选人。

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