Acquisition of a CryoProbe for a 600 MHz NMR Spectrometer

获取用于 600 MHz NMR 波谱仪的 CryoProbe

• 批准号: 7214931
• 负责人: DEREK S TAN
• 金额: $ 22.37万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-16 至 2010-04-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7214931
• 关键词: Alzheimer' s Disease; Anabolism; Anti-Infective Agents; Antibiotics; Biochemical; Biological; Biological Factors; COSY; Carbohydrates; Carbon; Chemistry; Chronic Myeloid Leukemia; Clinical Trials; Communicable Diseases; Complex; Core Facility; Diagnosis; Glycopeptides; HMQC; Human; Institutes; Libraries; Malignant Neoplasms; Molecular Chaperones; NOESY; Neurodegenerative Disorders; Numbers; Organic Synthesis; Pharmaceutical Chemistry; Property; Protons; ROESY; Range; Research; Research Personnel; Services; Siderophores; Standards of Weights and Measures; TOCSY; Therapeutic; Therapeutic Agents; Time; Vaccines; base; combinatorial chemistry; experience; gamma secretase; high throughput screening; instrumentation; kinase inhibitor; metabolic abnormality assessment; pathogenic bacteria; peptidomimetics; programs; radiotracer; research study; tool; tumor

DESCRIPTION (provided by applicant): The Sloan-Kettering Institute requests a dual 13C/1H CryoProbe (Cold Probe) to upgrade a 600 MHz NMR spectrometer. This instrumentation will be used by synthetic chemists who are developing new biological probes and therapeutic agents targeted to cancer, infectious diseases, and neurodegenerative disorders. Sloan-Kettering has a well-established and expanding chemistry program, but this instrumentation is not currently available to these chemists. The CryoProbe provides exceptionally high sensitivity (more than 4-fold higher than standard probe; more than 16-fold faster experiments), proton and carbon observation, and Z-gradients. The CryoProbe will provide significant new capabilities to these research teams, allowing rapid, routine, comprehensive analysis of (a) complex molecules available in only small quantities, such as natural product synthetic intermediates, carbohydrates, and peptidomimetics; and (b) large numbers of compounds synthesized during medicinal chemistry and combinatorial chemistry projects. In both cases, a full panel of otherwise time-consuming experiments can be performed (such as 13C-NMR, DEPT, J-RES, COSY, TOCSY, NOESY, ROESY, HMQC, HMBC, HETCOR), allowing complete structural identification and characterization. Previously inaccessible INADEQUATE experiments can also be considered. NIH-supported users include (1) Dr. Samuel Danishefsky, who is synthesizing natural products and glycopeptide vaccines with anti-tumor and anti-infective properties, several of which have been advanced to human clinical trials; (2) Dr. Gabriela Chiosis, who is developing modulators of the chaperones Hsp70 and Hsp90 to investigate their therapeutic potential; (3) Dr. Yueming Li, who is studying gamma-secretase function and inhibition to target Alzheimer's disease; (4) Dr. Bayard Clarkson, who is investigating kinase inhibitors as new treatments for chronic myeloid leukemia; (5) Dr. Derek Tan, who is developing diversity-oriented syntheses of natural product-based libraries for high-throughput screening against a broad range of biological targets and also developing new antibiotics targeting siderophore biosynthesis in pathogenic bacteria; (6) Dr. Steven Larson, who is developing new radiotracers for biochemical and metabolic studies to diagnose and treat cancer; and (7) Dr. Ouathek Ouerfelli, whose Organic Synthesis Core Facility provides chemistry services to more than 20 other NIH-supported investigators at Sloan-Kettering. The CryoProbe will be installed on a 600 MHz NMR spectrometer at the Sloan-Kettering Analytical NMR Core Facility, under the management of Dr. George Sukenick, who has 13 years of experience in directing this facility. Relevance: The requested instrumentation will be used by chemists at the Sloan-Kettering Institute to characterize synthetic molecules. Its extremely high sensitivity will greatly accelerate and assist their efforts to develop new biological tools and therapeutic agents to study and treat cancer, infectious diseases, and neurodegenerative disorders.

描述（由申请人提供）：Sloan-Kettering Institute要求双13 C/1H CryoProbe（冷探针）升级600 MHz NMR光谱仪。这种仪器将被合成化学家使用，他们正在开发针对癌症，传染病和神经退行性疾病的新生物探针和治疗剂。斯隆-凯特琳有一个完善的和不断扩大的化学计划，但这种仪器目前还没有提供给这些化学家。CryoProbe具有极高的灵敏度（比标准探针高4倍以上;实验速度快16倍以上）、质子和碳观察以及Z梯度。CryoProbe将为这些研究团队提供重要的新功能，允许快速，常规，全面分析（a）仅少量可用的复杂分子，如天然产物合成中间体，碳水化合物和肽模拟物;以及（B）在药物化学和组合化学项目中合成的大量化合物。在这两种情况下，可以进行一整套耗时的实验（如13 C-NMR、DEPT、J-RES、COSY、TOCSY、NOESY、ROESY、HMQC、HMBC、HETCOR），从而实现完整的结构鉴定和表征。以前无法实现的不充分的实验也可以考虑。NIH支持的用户包括：（1）Samuel Danishefsky博士，他正在合成具有抗肿瘤和抗感染特性的天然产物和糖肽疫苗，其中一些已经进入人体临床试验;（2）Gabriela Chiosis博士，他正在开发伴侣Hsp 70和Hsp 90的调节剂，以研究其治疗潜力;（3）李月明博士，他正在研究γ-分泌酶功能和抑制作用，以靶向阿尔茨海默病;（4）Bayard克拉克森博士，他正在研究激酶抑制剂作为慢性粒细胞白血病的新疗法;（5）Derek Tan博士，他正在开发基于天然产物的文库的多样性导向合成，用于针对广泛的生物靶标进行高通量筛选，并开发针对病原菌中铁载体生物合成的新抗生素;（6）Steven Larson博士，他正在开发新的放射性示踪剂，用于诊断和治疗癌症的生化和代谢研究;（7）Ouathek Ouerfelli博士，他的有机合成核心设施为Sloan-Kettering的其他20多名NIH支持的研究人员提供化学服务。CryoProbe将安装在Sloan-Kettering分析NMR核心设施的600 MHz NMR光谱仪上，由拥有13年指导该设施经验的乔治Sukenick博士管理。 相关性：斯隆-凯特琳研究所的化学家将使用所要求的仪器来确定合成分子的特性。其极高的灵敏度将大大加速和帮助他们开发新的生物工具和治疗剂，以研究和治疗癌症，传染病和神经退行性疾病。