Acquisition of a High Resolution Mass Spectrometer (LC-TOF-MS)

描述（由申请人提供）：斯隆-凯特林研究所申请一台高分辨率/高质量精度飞行时间质谱仪，该质谱仪具有超高性能液相色谱前端（LC-TOF-MS）。该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的生物探针和治疗剂。斯隆-凯特林有一个完善且不断扩大的化学项目，但这些化学家没有现场使用高分辨率质谱仪的机会。因此，样品目前被运送到外部服务设施，周转时间很长（长达28天），这延迟了研究进展，并且对于易于分解的样品不可行。此外，从LC-HRMS获益的实验，如混合物中未知成分的鉴定，目前还不可行。所要求的仪器具有高灵敏度、同时进行APCI和ESI电离、快速的正负离子模式切换、快速扫描速率、宽动态范围以及与单个样品成分的超高效液相色谱分离完全集成。现场使用这种新仪器将为斯隆-凯特林的化学家提供这些关键能力，使其成为常规和经济有效的基础。美国国立卫生研究院支持的用户包括(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，其中一些已进入人体临床试验；(2) Gabriela Chiosis博士，她正在开发Hsp70和Hsp90的调节因子，以研究它们的治疗潜力；(3)李月明博士，谁在学习？-分泌酶功能及其对阿尔茨海默病的抑制作用；(4) Bayard Clarkson博士，他正在研究激酶抑制剂作为慢性髓性白血病的新疗法；(5) Derek Tan博士，致力于开发以多样性为导向的基于天然产物的文库的合成，用于高通量筛选广泛的生物靶点，并开发针对致病菌中铁载体生物合成的新抗生素；(6) Steven Larson博士，他正在开发用于诊断和治疗癌症的生化和代谢研究的新型放射性示踪剂；(7) Ouathek ouerfeli博士，他的有机合成核心设施为斯隆-凯特林的其他20多名美国国立卫生研究院支持的研究人员提供化学服务。LC-TOF-MS仪器将位于Sloan-Kettering分析核磁共振核心设施，该设施目前为这些化学家提供低分辨率质谱服务，由George Sukenick博士管理，他在指导该设施方面有13年的经验。公共卫生相关声明：所要求的仪器将被斯隆-凯特林研究所的化学家用来表征合成分子。该仪器提供的新功能将大大加快和协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。

DESCRIPTION (provided by applicant): The Sloan-Kettering Institute requests a high resolution/high mass accuracy time-of-flight mass spectrometer with an ultra high performance liquid chromatography front end (LC-TOF-MS). This instrument 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 these chemists do not have on-site access to a high resolution mass spectrometer. As a result, samples are currently shipped to external service facilities with long turnaround times (up to 28 days), which delays research progress and is not feasible for samples that are prone to decomposition. Furthermore, experiments that benefit from LC-HRMS, such as identification of unknown components in mixtures, are not currently feasible. The requested instrument provides high sensitivity, simultaneous APCI and ESI ionization, fast positive/negative ion mode switching, fast scan rate, wide dynamic range, and full integration with ultra-HPLC separation of individual sample components. On-site access to this new instrument will provide these critical capabilities to chemists at Sloan-Kettering on a routine and cost- effective basis. 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 ?-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 LC-TOF-MS instrument will be located in the Sloan-Kettering Analytical NMR Core Facility, which currently provides low resolution mass spectrometry services to these chemists, and managed by Dr. George Sukenick, who has 13 years of experience in directing this facility. Public Health Relevance Statement: The requested instrument will be used by chemists at the Sloan- Kettering Institute to characterize synthetic molecules. The new capabilities provided by this instrument 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.