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Abstract: Heparan sulfates (HS) are complex polysaccharides belonging to the glycosaminoglycans (GAGs) family. HS are generally located on the cell surface and in the extracellular matrix from where they influence cells functions. GAGs are known to bind and regulate the function of a number of distinct proteins known as 'heparin binding proteins' (HBP) including chemokines, growth factors, enzymes, etc. It is known that the activity of HS depends on the presence in their chains of specifically sulfated sequences that can specifically regulate the activity of HBP. In the case of tumor development, an enhanced over-expression of heparanase, the enzyme that depolymerize HS, generates a variety of oligosaccharides that are released in the tumor matrix. At present, the structure and biological roles of these HS oligosaccharides are unknown. Although many tools to characterize GAGs exist, there is still a great need to develop new technologies allowing rapid and selective isolation of particular HS fragments. Here, we used the Molecular Imprinting Technology (MIT) to synthesize polymers with cavities capable to recognize a particular HS related pentasaccharide, used as template molecule. After synthesizing a library of polymers designed for template recognition, we selected a particular polymer able to specifically recognize the template oligosaccharide and validated its reproducible chemical synthesis. Studies to selectively extract the template oligosaccharide from HS extracts prepared from tumor tissue or tumor cells that over-express heparanase are in progress. The MIT technology is a promising tool for the specific selection, extraction and identification of endogenous HS oligosaccharides produced during tumor growth.
Template and target information: heperan sulfate, HS, HS-related pentasaccharide