Development of New Glycosyltransferase Inhibitors

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2' , 3' -Di-O-acetyluridine 5' -p-styrenesulfonate was synthesized by the reaction of 2' , 3' -di-O-acetyluridine with p-styrenesulfonyl chloride and polymerized. After removal of acetyl groups, the polymeric product was shown by NMR spectroscopy and gel permeation chromatography to be poly(uridine 5' -p-styrenesulfonate). This uridine-containing polymer was tested against the galactosyl transferase that synthesizes lactose in the presence of alpha-lactalbumin. The polymeric compound did inhibit the enzyme strongly. And this polymer inhibited also trehalose phosphate synthase which was purified from Mycobacterium.The adsorption of poly(uridine 5' -p-styrenesulfonate) on the polystyrene 96-well mutiplate was confirmed by ESCA measurements. On the poly(uridine 5' -p-styrene-sulfonate)-coated plate, adhesion of 3T3-L1 fibroblast which has galactosyl transferase on the cell surface was increased, compared with non-coated plate. And the increase in adhesive cell number was inhibited by the addition of EDTA, indicating that the cell adhesion needs metal ions. This result showed the 3T3-L1 fibroblast adhesion on the poly(uridine 5'-p-styrene-sulfonate)-coated plate may occur through the galactosyl transferase on the cell surface because this enzyme needs a divalent metal ion. On the other hand, Hem cell which does not have galactosyl transferase on the cell surface did not show the specific adhesion on the poly(uridine 5' -p-s tyrene-sulfonate)-coated plate. Moreover, it was suggested that the cell migration may occur by using the interaction betwecn galactosyl transferase on the cell surface of 3T3-L1 and poly(uridine 5'-p-styrene-sul fonate).