Shared Instrumentation Grant: LTQ Linear Ion Trap Mass Spectrometer

描述（由申请人提供）：糖缀合物在许多基本生物学过程中起关键作用，聚糖结构的变化与某些疾病和病症相关。归因于聚糖的大量生物活性部分是由于它们与聚糖结合蛋白或凝集素的相互作用，并且该相互作用通常以相对于聚糖结构的极大特异性发生。质谱法，特别是液相色谱质谱法（LC/MS），在聚糖结构分析中发挥着越来越重要的作用。在这里，我们要求资金购买Thermo Electron Finnigan LTQ XL离子阱质谱仪（MS），配有电喷雾源，配备Agilent 1200毛细管HPLC。该仪器将满足4个主要项目和12个次要项目的需求，这些项目由位于圣地亚哥的加州大学、欧文的加州大学、伯纳姆医学研究所、拉霍亚过敏和免疫学研究所以及Zacharon Pharmaceuticals，Inc.的多个用户执行。这些项目分为四大类：（1）N-和O-聚糖（H。冰冻湖帕森斯，W。Dillman，M. Fukuda，M.N. Fukuda，A. Varki）;（2）唾液酸异质性（A. Varki，D. Broide，V. Nizet）;（3）糖胺聚糖分析（J. Esko，B. Crawford，Y. Tor，Y.山口河瓦里尔河Gallo）;和（4）糖脂和糖苷（B.克劳福德河Aroian，M. Kronenberg，J. Esko）。所需仪器将存放在糖技术中心，并通过加州大学圣地亚哥分校的糖生物学研究和培训中心进行管理。将优先考虑一级项目和二级用户的充电基础上，与糖生物学社区的其他成员在一般情况下使用。该仪器将由Anup Datta博士（核心总监）、Roger Lawrence博士（项目科学家）和Sulabha Arabha博士操作和维护，他们都具有应用于聚糖的质谱分析经验。仪器运营、供应和服务合同的成本将由用户从充值收入中分摊。公共卫生相关性：聚糖的结构研究可以更好地了解它们如何与聚糖结合蛋白相互作用，这反过来又可以发现疾病和治疗药物的分子标记物。液相色谱-质谱联用技术是分析多糖和糖缀合物结构的最彻底的方法之一，比其他方法更稳定、灵敏和可靠。它在分析来自模式生物和患者的生物样品时特别有用，而不需要大量的高度纯化的样品。

DESCRIPTION (provided by applicant): Glycoconjugates play crucial roles in many fundamental biological processes, and changes in glycan structure correlate with certain diseases and disorders. The large number of biological activities attributed to glycans is due in part to their interaction with glycan-binding proteins or lectins, and the interaction often occurs with great specificity with respect to structure of the glycan. Mass spectrometry, especially liquid chromatography mass spectrometry (LC/MS), is playing an increasingly important role in the analysis of glycan structure. Here we request funds to purchase a Thermo Electron Finnigan LTQ XL ion trap mass spectrometer (MS) with electrospray sources, equipped with an Agilent 1200 capillary HPLC. The instrument will meet the needs of 4 primary projects and 12 secondary projects carried out by multiple users based at the University of California, San Diego, the University of California, Irvine, and The Burnham Institute for Medical Research, the La Jolla Institute for Allergy and Immunology, and Zacharon Pharmaceuticals, Inc. The projects fall into four major categories: (1) Analysis of N- and O-glycans (H. Freeze, L. Parsons, W. Dillman, M. Fukuda, M.N. Fukuda, A. Varki); (2) Sialic acid heterogeneity (A. Varki, D. Broide, V. Nizet); (3) Glycosaminoglycan analysis (J. Esko, B. Crawford, Y. Tor, Y. Yamaguchi, R. Warrior, R. Gallo); and (4) Glycolipids and glycosides (B. Crawford, R. Aroian, M. Kronenberg, J. Esko). The requested instrument will be housed in the Glycotechnology Core and administered through the Glycobiology Research and Training Center at the University of California, San Diego. Priority will be given to the primary projects and secondary users on a recharge basis, with use by other members of the glycobiology community at large when available. The instrument will be operated and maintained by Drs. Anup Datta (Core Director), Roger Lawrence (Project Scientist), and Sulabha Argade all of whom have experience in mass spectrometry as applied to glycans. The cost of instrument operation, supplies, and service contract will be shared by the users from recharge income. PUBLIC HEALTH RELEVANCE: Structural studies of glycans can lead to a better understanding of how they interact with glycan-binding proteins, which in turn can lead to the discovery of molecular markers for diseases and therapeutic agents. Liquid Chromatography Mass Spectrometry is one of the most thorough means for structurally analyzing glycans and glycoconjugates, being more robust, sensitive and reliable than other methods. It is particularly useful in analyzing biological samples from model organisms and patients, without necessitating large amounts of highly purified samples.