This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Glycoaminoglycans (GAGs) such as heparin and heparan sulfate (HS) are naturally occurring polydisperse linear polysaccharides that are heavily O- and N-sulfated. The interaction between GAGs and proteins can have profound physiological effects on hemostasis, lipid transport and adsorption, cell growth and migration and development. Binding of GAGs can result in the immobilization of proteins at their sites of production, regulation of enzyme activity, binding of ligands to their receptors and protection of proteins against degradation. Alteration in GAG expression has been associated with disease and, for example, significant structural changes have been reported in proteoglycans surrounding the stroma of tumors. It has been suggested that these alterations may support tumor growth and invasion. A challenging aspect of this field of HS research is to develop methods to analyze the structure of these compounds. The Esko laboratory has developed a highly sensitive method for analyzing the disaccharide subunit structure of glycosaminoglycan chains based on stable isotope tagging with aniline coupled with liquid chromatography-mass spectrometry. This highly sensitive technique can be used to study how the enzymes regulate the pattern of sulfation of the chains and for the development of lysosomal storage diseases, which have been associated with defects in the catabolism of HS such as mucopolysaccharidoses (MPS) 1, II, IIIA, B and C. It is to be expected that the use of HS oligosaccharide standards will facilitate quantification of HS part structures.
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