Mass Spectrometry of Metal-Coordinated Oligosaccharides

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DESCRIPTION (provided by applicant): The broad goal of this competing renewal focuses on glycosaminoglycan separation, purification and complete chemical characterization as it pertains to heparin and HS complexation to various inflammatory chemokines. Methods will be developed to separate, purify and identify glycosaminoglycan (GAG) binders of three specific Rheumatoid Arthritis associated chemokines using chromatography, ion mobility mass spectrometry (IM-MS) and CID-MS. Complexation of GAG binders to their chemokine counterparts will be investigated by MS with the monomer, dimer and tetramer assemblies measured using IM-MS. These studies will be paired with the compositional analysis of GAG in sera from women with Rheumatoid Arthritis in the pre- and postmenopausal age range to determine health benefits of HRT and its correlation with GAG composition. The three specific aims are: Specific Aim 1: GAG composition in Human Serum, Specific Aim 2: Chromatographic preparation, separation, identification and complexation of GAG libraries with Chemokines, and Specific Aim 3: Ion Mobility MS and X-ray crystallography of Chemokine and GAG binders. The major areas proposed are interwoven in such a way that methods development, biotechnology and application to biologically relevant systems are the cohesive elements that bind the proposed research together.