It is strongly suggested that alteration in the levels and specificity of glycosyltransferase may cause alterations in the carbohydrate composition of cell surface glycoconjugates. In recent years the possibility of some glycosyltransferases acting as tumor markers has become apparent. In this program we have been concentrating our efforts on the study of human fucosyl, galactosyl and sialyltransferases. Well-defined carbohydrate structures are important tools for the study of glycosyltransferases and we plan to continue to employ a series of carbohydrate compounds to determine the specificity of these enzymes. The glycosidic linkage from a sugar nucleotide donor to the acceptor, formed by the catalytic reaction of a glycosyltransferase, will be established by various procedures which also includes the use of specific glycosidases. Our synthetic capability also provides reference compounds for confirming the structure of enzymatic products. We plan to elucidate the biosynthetic pathway of certain tumor- associated antigens, e.g. glycoconjugates with Lex determinants and sialylated Lex determinants, whereby our synthetic fragments which occur as a part of such antigens play a key role. Our specificity studies on glycosyltransferase from tumor tissue and normal tissue will enable us to see if the enzymes from tumor tissue have broad specificity or not. Moreover, our investigations should lead to the discovery of a highly specific acceptor for a specific type of glycosyltransferase and our synthetic modified analogs will be useful for the assay of a single type of glycosyltransferase. Utilizing such specific and unique acceptors, levels of the glycosyltransferase in sera or saliva of healthy individuals and in specimens from cancer patients will be examined. Precisely, this program provides a systematic approach primarily for the biochemical studies of three types of glycosyltransferases and purification of only selected enzyme activities are included.
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