Shared Instrumentation Grant: LTQ Linear Ion Trap Mass Spectrometer

描述(申请人提供)：糖共轭化合物在许多基本的生物过程中起着关键作用，而糖结构的变化与某些疾病和障碍相关。多糖的大量生物活性部分归因于它们与糖结合蛋白或凝集素的相互作用，而这种相互作用往往与多糖的结构具有很强的特异性。质谱学，特别是液-质联用(LC/MS)在糖链结构分析中发挥着越来越重要的作用。在此，我们申请资金购买一台Thermo Electron Finnigan LTQ XL离子陷阱质谱仪(MS)，配有安捷伦1200毛细管高效液相色谱仪。该仪器将满足加州大学圣地亚哥分校、加州大学欧文分校和伯纳姆医学研究所、拉霍亚过敏和免疫学研究所以及Zacharon制药公司的多个用户进行的4个初级项目和12个次级项目的需要。这些项目分为四大类：(1)N-和O-多糖的分析(H.From，L.Parsons，W.Dillman，M.Fukuda，M.N.Fukuda，A.Varki)；(2)唾液酸不均质性(A.Varki，D.Broide，Nizet)；(3)糖胺聚糖分析(J.Esko，B.Crawford，Y.Tor，Y.Yamaguchi，R.Warrior，R.Gallo)；和(4)糖脂和糖苷(B.Crawford，R.Aroian，M.Kronenberg，J.Esko)。所要求的仪器将被安置在糖技术核心中，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。将在充值的基础上优先考虑主要项目和次级用户，可供糖生物界的其他成员使用。该仪器将由Anup Datta博士(核心主任)、Roger Lawrence博士(项目科学家)和Sulabha Argade博士操作和维护，他们都具有应用于多糖的质谱学经验。仪器运行费用、用品费用和服务合同费用由用户从充值收入中分摊。与公共健康相关：对多糖的结构研究可以更好地了解它们如何与糖结合蛋白相互作用，这反过来又可能导致发现疾病和治疗剂的分子标记。液-质联用法是目前分析糖链和糖结合物结构最彻底的手段之一，与其他方法相比具有更好的稳定性、灵敏度和可靠性。它在分析来自模型生物体和患者的生物样本时特别有用，而不需要大量高度纯化的样本。

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.