Star-shaped polypeptide/glycopolymer biohybrids composed of poly(gamma-benzyl L-glutamate) and poly(D-gluconamidoethyl methacrylate), exhibiting controlled molecular weights and low polydispersities, were synthesized by the combination of ring-opening polymerization of gamma-benzyl-L-glutamate N-carboxyanhydride and the direct atom transfer radical polymerization of unprotected D-gluconamidoethyl methacrylate glycomonomer. These biohybrids were characterized in detail by means of FTIR, H-1 NMR, gel permeation chromatography, differential scanning calorimetry, and wide angle X-ray diffraction. Independent of weight fraction of hydrophilic glycopolymer segment, the biohybrids self-assembled into large spherical micelles in aqueous solution, which had a helical polypeptide core surrounded by a multivalent glycopolymer shell. The deprotected poly(L-glutamate)/glycopolymer hybrid exhibited a pH-sensitive self-assembly behavior, and the average size of the nanoparticles decreased gradually over the aqueous pH value. Moreover, whatever these biohybrids existed in unimolecular level or glycopolymer-surfaced nanoparticles, they had specific biomolecular recognition with Concanavalin A compared with bovine serum albumin. Furthermore, star-shaped biohybrids showed a higher doxorubicin loading efficiency and longer drug-release time than linear analogues. This potentially provides a platform for fabricating targeted anticancer drug delivery system and studying glycoprotein functions in vitro. (C) 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 2009-2023, 2009