Acquisition of a CryoProbe for a 600 MHz NMR Spectrometer

描述(由申请人提供)：斯隆-凯特琳研究所要求使用双13C/1H CryoProbe(冷探头)升级600 MHz核磁共振光谱仪。这种仪器将由合成化学家使用，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-凯特林有一个完善的和不断扩大的化学课程，但目前这些化学家还不能使用这种仪器。CryoProbe提供极高的灵敏度(比标准探头高4倍以上；实验速度快16倍以上)、质子和碳观测以及Z梯度。CryoProbe将为这些研究团队提供重要的新能力，使其能够快速、常规、全面地分析(A)仅有少量复杂分子，如天然产品合成中间体、碳水化合物和肽类仿制品；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，都可以进行一整套耗时的实验(例如13C-核磁共振、DEPT、J-RES、COSY、TOCSY、NOESY、ROESY、HMQC、HMBC、HETCOR)，从而实现完整的结构鉴定和表征。以前无法进入的不充分的实验也可以被考虑。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品和糖肽疫苗，其中几个已进入人体临床试验；(2)Gabriela Chisis博士，他正在开发伴侣Hsp70和Hsp90的调节剂，以研究其治疗潜力；(3)李月明博士，他正在研究伽玛分泌酶功能和抑制阿尔茨海默病的作用；(4)Bayard Clarkson博士，他正在研究将激酶抑制剂作为慢性髓系白血病的新疗法；(5)Derek Tan博士，他正在开发天然产物文库的以多样性为导向的合成，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，他正在为诊断和治疗癌症的生化和代谢研究开发新的放射示踪剂；及(7)Ouathek Ouerfelli博士，他的有机合成核心设施为斯隆-凯特琳的其他20多名NIH支持的研究人员提供化学服务。CryoProbe将安装在斯隆-凯特琳分析核磁共振核心设施的600 MHz核磁共振光谱仪上，由乔治·苏肯尼克博士管理，苏肯尼克博士在指导这一设施方面拥有13年的经验。 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表征合成分子。其极高的灵敏度将极大地加速和帮助他们开发新的生物工具和治疗剂来研究和治疗癌症、传染病和神经退行性疾病。

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.