Synthesis of Glycopolymers Bearing Mannaric Pendants as Inhibitors on the β-Glucuronidase Activity: The Inhibition Mechanisms of Mannaric- and Glucaric-Compounds

A new styrene derivative having D-mannaric moiety, N-p-vinylbenzyl-D-mannaramic acid (VB-D-ManaH, 8) was synthesized though the ring-opening reaction Of D-mannaro-1,4:6,3-dilactone (D-MDL) with p-vinylbenzylamine. VB-D-ManaH was copolymerized with acrylamide (AAm) to give novel polymers having D-mannaric moiety in the pendants, P(VB-D-ManaH-co-AAm), 10. The resulting glycomonomer and polymer (8 and 10) bearing D-mannaric pendants were found to inhibit the beta-glucuronidase activity, although the inhibition ability of the corresponding saccharodilactone (D-MDL) was known to be low. Additionally, the inhibition ability of P(VB-D-ManaH-co-AAm), 10, was almost the same as that of the glycopolymer having D-glucaric pendants, P(VB-6-D-GlcaH-co-AAm), 1, which was one of the most effective inhibitors for beta-glucuronidase, reported in our previous work. Thus, 10 and 8 may be the first D-mannaric strong inhibitors to the beta-glucuronidase activity. The Lineweaver-Burk plot suggested that the inhibition mechanisms of 10 and 8 were more complicated than in the case of the competitive and uncompetitive inhibition of N-p-(vinylbenzyl)-6-D-glucaramic (11) and N-p-(vinylbenzyl)-1-D-glucaramic acids (12), respectively. (C) 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 2032-2042, 2009