No abstract

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.

Here we report the chemoenzymatic synthesis and recognition function of glycoconjugate polymers carrying nonreducing disaccharides [α‐D‐glucopyranosyl‐(1‐1)‐α‐D‐glucopyranoside (trehalose) and α‐D‐galactopyranosyl‐(1‐1)‐α‐D‐glucopyranoside (Gal‐type trehalose)]. The lipase‐catalyzed esterification of the disaccharides with divinyl sebacate is completely selective at the primary Glc 6‐OH position of trehalose and at the Gal 6‐OH position of Gal‐type trehalose. The resultant vinyl esters can be polymerized to yield glycoconjugate polymers with poly(vinyl alcohol) backbones. The interactions of the glycoconjugate polymers with lectins (concanavalin A and Bandeiraera simplicifolia) are amplified because of the glycocluster effect. The polymer carrying pendant α‐D‐galactopyranosyl‐(1‐1)‐α‐D‐glucopyranoside shows inhibition activity against Shiga toxin‐1 based on a stereochemical structure similar to that of globosyl Gb2 disaccharide. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4598–4606, 2004

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.

No abstract