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Research paper : Development of basic tools for glycoscience and their application to cancer diagnosis (H. Narimatsu)−202−Synthesiology - English edition Vol.5 No.3 (2012) be some important functions in the existence of glycan molecules. However, functional analysis of glycan-related proteins is often avoided by many scientists, as there is no appropriate basic technology for analysis.The whole human genome sequencing was completed 11 years ago, and major attention was given to proteomics (comprehensive analysis of proteins) taking the resultant genome sequences as the templates. We were sure that this flow of scientific approach will be directed toward the comprehensive analysis of glycoproteins, the final form of functional molecules. It would require development of the basic technology tools for glycoscience. By means of such tools, analysis of glycan functions would be enhanced under the concept of glycoproteome. We were aiming for the goal of glycoproteomics as the biomedical application, in other words, diagnostic and therapeutic technologies. 2 About glycans“Glycans are like clothing for cells and proteins” (Fig.1). Characteristics of glycans as summarized are expected to be applied in many fields.(1)Sequential structures of glycans are dramatically altered along with differentiation, maturation, and activation of cells. If a normal cell becomes a cancerous cell, the cell will dedifferentiate and its glycan structures will be widely modified as well. Such alterations would make glycans the best prospective cancer markers and be applicable to regenerative medicine. Glycan structures change regularly along with the direction of differentiation, which supposed to be useful in the lineage determination of cultured cells. The germ cells mature and differentiate most rapidly among other cells. Glycans of sperm and ova indicate fast and amazing changes, which suggest an important role of glycans in maturation.Moreover, glycan structures also react and change quickly upon activation and inactivation of cells. Cells related to the immune system show alterations of glycan structures along with their activation and inactivation.(2)Glycan structures are varied by the derivate tissue of the carrier protein. As an example, transferrin is produced by both the liver cell and choroid plexus, but the glycan structures of transferrin derived from different origins are different but their carrier proteins are the same. Thus the origin of a protein can be detected based on its glycan structure. Moreover, expression levels of certain sialyltransferases and sulfotransferases often increase dramatically in cancerous cells, and as a result, many glycoproteins are sialylated or sulfated. The negative charge of the cancerous cell surface increases due to the increase of sialic acid and the sulfate group. This indicates that controlling only a few glycotransferases would affect functions of abundant glycoproteins. As a result, characteristics of cells are widely affected by glycotransferases.(3)Glycan structures in a variety of glycoproteins produced by one particular cell vary widely. Despite the fact that the glycoproteins derived from the same cell have the same expression pattern of glycosyltransferases, each kind of glycoproteins has a characteristic glycan structure, and the mechanism for this system has not yet been clarified.(4)Glycans have individual specificity. A representative example is the blood type. Not only the ABO blood group system, but also Lewis, P, and Ii systems are based on AgingQualified as a biomarker(disease/differentiation/function marker)IndividualdifferenceAbnormal cell(Disease)SenescentcellMature cell(Differentiated cell)Immature cell(Stem cell, undifferentiated cell)• Reflecting cell conditions (development and differentiation, disease conditions)• Having various functions depending on the cell conditionsSpecies specificityOrgans specificityDevelopmentFunctionResponseCell developmentdifferentiationGlycans are …cell-specific DifferentiationStimulationFig. 1 Glycans are like clothing for cells and proteins

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