Mapping the Carbohydrate Specificity Profiles of Toxic and Applied Lectins by Carbohydrate Structural Units, Simple Clusters and Natural Polyvalent Glycotopes

Studies on the affinity of toxic and applied lectins and carbohydrate binding proteins from edible mushrooms, seeds, food and Chinese folk medicines or herbs, such as Solanum tubersum (potato), Arachis hypogea (peanut), Horduem vulgarie, Vaccaria pyramidata and Trichosanthis kirilowii, for glycotopes should provide a better understanding of the functional role of lectins and complex carbohydrates in life processes. Lectins can be used to evaluate the different distributions of complex carbohydrates in cancer, normal cells, and tissues at the molecular level. These studies also provide important information concerning the development of analytical reagents for serodiagnosis and treatment (immuno-drugs). During the past decades, many toxic and applied lectins have been tested for their medical values. However, knowledge of the binding properties of lectins, such as Viscum album (ML-I, ML-II, ML-III), Abrin-a, Abrin-b, Abrin-c, and Momordica charantia is limited. In previous years, we identified two lectins - abrin-a and ML-I that have affinity for Galαl→4Gal, a receptor of the uropathogenic E. coli toxin and Shiga toxin (Wu et al., Biochim. Biophys. Acta, 1243, 124-128, 1995). We also reported on “Effect of Polyvalencies of Glycotopes on the Binding of Lectins” (Wu et al., Biochemical J., 371, 311-320, 2003; Glycobiology, 16, 524-537, 2006; Glycoconjugate J., 24, 591-604, 2007). In this proposal, the binding properties of toxic and applied lectins will be studied by a series of immunochemical methods. The methods to be used include quantitative precipitin, and precipitin inhibition assays, hemagglutination and hemagglutination-inhibition assays, enzyme linked lectino-sorbent assay (Wu et al., J. Biomed. Sci., 11, 874-885, 2004; Mol. Immunol., 43, 1700-1715, 2006; Glycobiology, 17, 165-184,2007). In the first part of this plan, lectins of biomedical importance will be characterized by the interaction of lectins with established compounds (glycoproteins and polysaccharides). The binding properties of these lectins will be expressed by mammalian glyco-structural units (J. Biomed. Sci., 10, 676-688, 2003; Biochimie, 86 317-326, 2004; Lectin- Analytical Technologies (Ed. CL Nilsson), Elsevier, Amsterdam, NL, 167-192, 2007). In the second part of this work, carbohydrate antigens and/or lectin active complex carbohydrates that are related to cancer will be isolated and their antigenic and/or lectin determinants will be prepared and characterized. Their binding and structural differences will be compared. The third part of this study pertains to the characterization of receptors (glycotopes) on target cells and the most complementary structural units will be illustrated. Once the binding properties of lectins are mapped, the results will be included in an updated guide for carbohydrate specificities of applied lectins, as shown in Adv. Exp. Med. Biol., 491, 551-585, 2001 and J. Biomed. Sci., 10, 676-688, 2003; Lectin- Analytical Technologies (Ed. CL Nilsson), Elsevier, Amsterdam, NL, 167-192, 2007, and edited as lectin index.

Project ID:PC9709-1349
External Project ID:NSC97-2628-B182-002-MY3