Glycotopes in Glycans and Their Polyvalent Structures for the Elucidation of the Molecular Recognition Mechanisms

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 glycans 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 major directions will be pursued. Basically, several ongoing projects will be continued, especially studies on the carbohydrate 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 (Gal3GalNAc1Ser/Thr), Tn (GalNAc1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 (laminin, transferrin, fibrinogen and lactoferrin etc.) are being 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 developed; glycotope structures of sialyl Lex, sialyl Lea, Lex, Ley and a novel glycotope (GlcNAcα1→4Gal) among human ovarian cyst gps (HOC #59) and a glycan array for analysis of glycan – lectin/Ab interactions should be two the major goals to be accomplished. At the same time, new topics of medical importance in Taiwan are being evaluated. These include defining the roles of carbohydrate structural changes in intraductal papillary mucinous neoplasm of the pancreas (IPMN), hepatic bile mucin, cardiac cancer and retinal detachment. Some of the subjects related to differentiation of the distribution and mobility of cell surface or secreted glycoproteins between normal and malignant/diseased cells, structural elucidation of glycotopes of tumor markers (MUC, CA199, CA125 and AFP, etc.) from serum/cancers, and biological functions and carbohydrate specificities of C-reactive protein (CRP) are also considering to be integrated into our program for which we will consult with pathologists, physicians, and related experts.

Project ID:PC10108-0744
External Project ID:NSC101-2320-B182-011