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酵素唾液酸化 Globo-系列醣體
Thesis

酵素唾液酸化 Globo-系列醣體

郭力禎
Masters, 國立清華大學, 化學系
2014

Abstract

酵素 唾液酸 globo enzyme sugar sialic acid
Studies indicate DSGb5 and SSEA4 are tumor associated antigens. Globo-series ganglioside may be important epitopes involving in biological events. In addition, sialic acids are usually decorated at the terminal position of glycan chain in nature. It is not surprising that sialosides play critical roles in diverse biological process. Sialic acid-binding Ig-like lectins (Siglecs) possess different specific recognition sites to different sialic acid containing ligands. Specific lock-and-key recognition can stimulate or inhibit immunnal signals. Recent studies have showned Siglecs may serve as therapic candidates. Furthermore, it is proven that synthetic glycan ligands are valuable tools for elucidating relationship between siglec-ligand interaction and disease. Due to the high regio- and stereo-selectivity of enzymatic synthesis, researches of enzymes as catalysts have grown rapidily and becomed promising methods in oligosaccharide synthesis. In this thesis, glycosyltransferase (LgtD from Haemophilus influenzae) and uridyltransferase (GlmU from E. coli) were chosen as key enzymes and used to construct globoside. We assembled LgtD, GlmU and the other 8 kinds of enzymes, including kinase, uridyltransferase, glycosyltransferase, and sialyltransferase for complicated sialylated carbohydrate synthesis. A globo-sialoside library, α-2,3-sialyl-Gb3, α-2,6-sialyl-Gb3, α-2,3-sialyl-Gb4 and α-2,6-sialyl-Gb4, was successfully establish by using different source of sialyltransferases. These molecules can serve as starting materials for further carbohydrate bioactivity researches.

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