GLYCOBIOLOGY OF SULFATED GLYCOCONJUGATES IN CANCER

最近认识到癌症相关的糖脂和

Recent recognition of canceir-associated glycolipids and glycoproteins containing a sulfate residue (or residues) raises very important and interesting questions: Is aberrant sulfation a characteristic of certain malignancies; what type of sulfotransferases are involved in the expression of these sulfoglycoconjugates? This project centers at the glycobiology of sulfosaccharides in order to seek answers to these questions. The prime interest is in the biochemical aspects, and in the synthesis of carbohydrate structures required for these studies. Under study are different sulfotransferases such as: (a) Galactose 3-0-sulfotransferase, which acts upon Gal 0 1-3GaINAca-linked compounds. The existence of this enzyme activity in human ovarian tissues and human spleen has already been demonstrated in an earlier phase of this research. (b) Sulfotransferase capable of acting on GaIPl-4GlcNAc and Galpl-3GlcNAc to give SE-3GaI0l-4GIcNAc; and SE-3Gal0I-6GIcNAc, respectively. Human colon tissues contain this enzyme. (c) 6-0-Sulfotransferase involved in the assembly of the 6'-sulfated Lewis (x)moiety [NeuAca2-3(SE-6Gal)pl-4(Fucal-3)GlcNAc]. (d) Sulfotransferase, which acts on G1cNAc0I-3GaIP1-OMe to give SE-6GIcNAc0l-3GaI0l-OMe. Different tumor cell lines and both normal and cancerous human tissues are utilized as a source material for screening and demonstrating the existence of sulfotransferase. Among these sources, those displaying appreciable activity become candidates for further study. The synthetic saccharides having sulfate situated at different positions (isomeric sulfated saccharides) are expected to be particularly useful as reference compounds for the characterization and analysis of sulfotransferase products. The identification of sulfotransferase activities will shed new light on the biosynthetic pathways of glycoconjugates, especially those glycoconjugates containing sulfate, fucose and sialic acid. These studies will provide information toward the synthesis of target ligands for cell- adhesion (selectin) molecules.