Molecular Glyco-biology of Bioactive Structural Units in Glycans (I)

Knowledge of the structures and binding properties of antigenic determinants and glyco-active sites of complex carbohydrates will contribute to a better understanding of the functional roles of these complex carbohydrates at the molecular level, and provide us with valuable information about the following aspects: (a) in-depth understanding life process and mechanism of infections and genetic disorders; (b) developing vaccines or drugs to prevent infection & inflammation; (c) producing new reagents to detect cancer; and (d) improving serodiagnosis. In this proposal, two directions will be pursued. Basically, several ongoing projects will be continued, such as studies on the carbohydrate side chains of blood group A, B, H, Lea, Leb, Lex, Ley, Ii, sialyl Lex and sialyl Ley active glycoproteins, prepared from human ovarian cyst fluid, will give us valuable clues explaining the mechanisms of oncogenesis and biosynthesis of blood group determinants; structural concepts of the carbohydrate moieties of epithelial mucus glycoproteins and Tamm- Horsfall glycoprotein are necessary for explaining their function as a barrier to protect from microbial invasion at the molecular level; comparisons of the chemical structure and binding properties of T (Galb1®3GalNAca1®Ser/Thr), Tn (GalNAca1®Ser/Thr) and other determinants of the glycoproteins (glycophorins & band III) of human erythrocytes and of the glycoproteins of cancer and mammalian epithelial secretions give us ideas about the possible existence of unique epitopes for differential diagnosis; Structures and functions of N-linked glycan in salivary mucin (Rat sublingual gp. vs. Porcine salivary mucin) and binding properties of N-glycans (Lactoferrin, transferrin, fibrinogen and laminin etc.) will be investigated; the immunochemical characterization of O-antigens of endotoxins, providing a valuable guide for developing better reagents for serological tests and for producing new vaccines will be established; glycotope structures of sialyl Lex in human ovarian cyst gps (HOC #350) and a glycan array for analysis of glycan-binding specificity will be the major goals to be accomplished. At the same time, new topics of medical importance in Taiwan are being evaluated in our laboratory. These include defining the roles of carbohydrate structural changes in retinal detachment, neovascularization and associated ocular diseases, glycotopes of (AFP) tumor markers from (liver) cancers. Some of the subjects related to functional roles of selectins and intergrins, structural elucidation of metabolic and genetic disorders, such as metabolite changes in Fabry's disease, carbohydrate changes of the carbohydrate moiety of glycosphingolipids and lipoproteins in aging and neural dysfunction, etc., plan to be integrated into our program for which we will consult with pathologists, physicians, and experts.

Project ID:PC9408-2042
External Project ID:NSC94-2320-B182-044