Well-defined pH-responsive glycopolypeptides were prepared by polymer-analogous aqueous amide coupling of D-glucosamine to poly(alpha,L-glutamic acid) (PGA) using the coupling agent 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) without any organic solvents, additives, or buffers. Degrees of substitution (DS) up to 80% can be achieved, and the DS is adjustable by the molar ratio of DMT-MM to PGA repeating units. Successful glycosylation of both low MW and high MW PGA was confirmed by H-1 NMR and FTIR spectroscopy as well as by an enhanced solubility at low pH. CD spectroscopy revealed that glycosylated PGAs with a DS up to 0.63 are able to undergo a pH-responsive and reversible helix-coil transition. However, for polymers with higher DS no transition occurs. A comparison with PGAs functionalized with monoethanolamine showed that the low helicity at high DS is not a steric effect due to the bulky sugar moieties, but a solvation effect. Preliminary turbidimetric tests with the lectin Concanavalin A indicate a biological activity of these glycosylated polypeptides. (C) 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3925-3931