AbstractTwo kinds of new glycopolymers, (P(VB‐1‐GlcaH‐co‐AAm), 9) and (P(VB‐1‐Glco‐co‐AAm), 10), were synthesized through the radical copolymerization of styrene derivatives bearing pendant D‐glucaric and D‐gluconic moieties, N‐(p‐vinylbenzyl)‐1‐D‐glucaramide (VB‐1‐GlcaH, 7), and N‐(p‐vinylbenzyl)‐D‐gluconamide (VB‐1‐Glco, 8), with acrylamide (AAm). Glycopolymer 9 bearing the pendant glucaric moiety at the first position inhibited the hydrolysis of a model compound for xenobiotics‐β‐glucuronide conjugates, p‐nitrophenyl β‐D‐glucuronide, uncompetitively, in contrast to the competitive inhibition in the presence of the corresponding isomeric glycopolymer bearing the pendant D‐glucaric unit at the sixth position (P(VB‐6‐GlcaH‐co‐AAm), 3) reported in our previous article. On the other hand, another copolymer 10 bearing the gluconic moiety was found not to inhibit the hydrolysis as well as the corresponding copolymer bearing pendant gulonic unit (P(VB‐6‐Glco‐co‐AAm), 4). These results indicate that the hydrolysis is influenced not only by existence of pendant carboxyl units but also by the direction on the linkage of the glyco‐units to the polymer frame. Therefore the configurational position of hydroxy groups in pendant glyco‐units in macromolecular inhibitors may be essential for the interaction with β‐glucuronidase. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 4895–4903, 2006