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.
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.
| Lawrence, Roger; Brown, Jillian R; Lorey, Fred et al. (2014) Glycan-based biomarkers for mucopolysaccharidoses. Mol Genet Metab 111:73-83 |
