Glycoconjugate polymers with poly(vinyl alcohol) (PVA) backbone were synthesized via a chemoenzymatic method. The sugar alcohols of maltose and lactose were submitted to transesterification in the presence of lipases. The esterification was achieved with high selectivity and yield, and the resulting maltitol and lactitol 6-vinyl sebacates were polymerized by a conventional radical initiator with hydrogen peroxide and ascorbic acid. The glycoconjugate polymers carrying alpha-glucose and beta-galactose as recognition signals showed the biological activity such as lectin recognition abilities and hepatocyte adhension. The biodegradability of these polymers was modest but higher than PVA.

We describe herein the relationship between the spatial arrangement of self-organized galactose clusters and lectin recognition. beta-Galactose-modified deoxyuridine phosphoramidite was synthesized and applied to solid-phase synthesis to provide 18-, 20-, and 22-mers of site-specifically galactosylated oligodeoxynucleotides (Gal-ODNs). These Gal-ODNs were self-organized through hybridization with the corresponding 18-, 20-, and 22-mers of half-sliding complementary ODNs (hsc-ODNs) to give periodic galactoside clusters. The self-organization of ODNs was confirmed by size exclusion chromatography and gel electrophoresis. The binding of the Gal-clusters to the FITC-labeled RCA(120) lectin was analyzed by monitoring the change in fluorescence intensity. The assembly of 20-mer Gal-ODN with the 20-mer hsc-ODN was strongly and cooperatively recognized by the lectin. The 18-mer assembly was bound more weakly and less cooperatively, and the 22-mer assembly was minimally bound to the lectin. RCA(120) lectin recognized not only the density of galactoside residues, but also the spatial arrangement. The size of the Gal cluster was estimated from the association constant of Gal-ODN with hsc-ODN. The relationship between lectin-recognition and Gal-cluster size is also discussed.

We report a novel strategy for micropatterned carbohydrate displays on Si substrates. This method exploited the hydrophobic-hydrophilic microfabrication by photolithography of ODS-SAM on Si substrates and the subsequent selective self-assembly of glycoconjugate polymers onto the hydrophobic regions. Protein micropatterning by molecular recognition on the carbohydrate substrates was also successful.

published as an Advance Article on the web 4th August 2003Glycoconjugate polymers with biodegradable poly(vinyl alcohol) (PVA) were synthesized via lipase-catalyzed transesterification of sugar alcohols (maltitol and lactitol) with divinyl dicarboxylates and subsequent radical polymerization. The conversion and chemoselectivity in transesterification were dependent on the lipases, the sugar alcohols, and the alkyl chain length of the dicarboxylates. Chemoselective esterification was attained in the presence of lipase from Candida antarctica (lipase CA) to give maltitol 6-vinyl sebacate, lactitol 6-vinyl sebacate, and lactitol 6-vinyl adipate in high yields. Polymerization of these vinyl esters with hydrogen peroxide/ascorbic acid as initiator gave glycoconjugate polymers. These polymers were suggested to take micellar conformations in water and to bind strongly to specific lectins (concanavalin A or RCA 120 ). The biodegradabilities of these polymers were modest but higher than PVA. This simple synthesis will be useful to develop various glycoconjugate polymers with high biological activities due to the multivalent glyco-cluster effect and biodegradability due to their PVA backbone and ester linkage.

A polymeric aminoglycoside was prepared by a facile chemoenzymatic reaction. Boc‐protected aminoglycoside, amikacin, was chemoselectively esterified with divinyl sebacate at a hydroxyl group in the C6″ position by protease from Bacillus subtilis. The resulting 3,6′,3″,4‴‐tetra‐N‐Boc‐6″‐O‐vinyl sebacate was copolymerized with maltitol 6‐vinyl sebacate to yield a polymeric amikacin. The polymeric amikacin showed a modest inhibitory effect on in vitro protein synthesis, and a little antibiotic activity in minimum inhibitory concentration (MIC) assay in the presence of protease.