Synthesis of sulfated phenyl 2-acetamido-2-deoxy-D-galactopyranosides.4-O-Sulfated phenyl 2-acetamido-2-deoxy-beta-D-galactopyranoside is a competitive acceptor that decreases sulfation of chondroitin sulfate by N-acetylgalactosamine 4-sulfate 6-O-su

摘要

We have previously cloned N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase (GalNAc4S-6ST),which transfers sulfate from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to the C-6 hydroxyl group of the GalNAc 4-sulfate residue of chondroitin sulfate A and forms chondroitin sulfate E containing GlcA-GalNAc(4,6-SO_4) repeating units.To investigate the function of chondroitin sulfate E,the development of specific inhibitors of GalNAc4S-6ST is important.Because GalNAc4S-6ST requires a sulfate group attached to the C-4 hydroxyl group of the GalNAc residue as the acceptor,the sulfated GalNAc residue is expected to interact with GalNAc4S-6ST and affect its activity.In this study,we synthesized phenyl alpha- or -beta-2-acetamido-2-deoxy-beta-D-galactopyrano-sides containing a sulfate group at the C-3,C-4,or C-6 hydroxyl groups and examined their inhibitory activity against recombinant GalNAc4S-6ST.We found that phenyl beta-GalNAc(4SO_4) inhibits GalNAc4S-6ST competitively and also serves as an acceptor.The sulfated product derived from phenyl beta-GalNAc(4SO_4) was identical to phenyl beta-GalNAc(4,6-SO_4).These observations indicate that derivatives of beta-D-GalNAc(4SO_4) are possible specific inhibitors of GalNAc4S-6ST.