Applications of chromatography and spectroscopy to heparin and heparan sulfate glycomics.

摘要

Glycomics, similar to genomics and proteomics, deals with the structure and function relationship of glycosaminoglycans (GAGs). Heparin and the structurally similar polysaccharide, heparan sulfate are the most important polysaccharides in GAG family. During the past 25 years, heparin and heparan sulfate have been recognized for their numerous important activities, many of which are independent from their well understood anticoagulant activity. These activities mediate various physiological and pathophysiological processes, thus understanding the roles of heparin and heparan sulfate might lead to potential therapeutic applications beyond their use as anticoagulant drugs.;However, the structural analysis of heparin and heparan sulfate is still extremely challenging as they have a high level of structural complexity. Chromatography and spectroscopy are the most important techniques for the separation and analysis of GAGs. This doctoral work discusses the study of heparin and heparan sulfate glycomics using improved chromatographic and spectroscopic techniques. The role of heparan sulfate in malaria was determined using high performance liquid chromatography (HPLC) and surface plasmon resonance (SPR); the structure and conformation of anticoagulant heparin were determined by utilizing 3-dimensional nuclear magnetic resonance (3D-NMR); also novel internal standards were developed for quantitative disaccharide analysis using liquid chromatography -- 2-dimensional mass spectrometry (LC-MS/MS).