The synthesis of arborescent polymers with poly(-benzyl L-glutamate) (PBG) side chains was achieved through successive grafting reactions. The linear PBG building blocks were produced by the ring-opening polymerization of -benzyl L-glutamic acid N-carboxyanhydride initiated with n-hexylamine. The polymerization conditions were optimized to minimize the loss of amino chain termini in the reaction. Acidolysis of a fraction of the benzyl groups on a linear PBG substrate and coupling with linear PBG using a carbodiimide/hydroxybenzotriazole promoter system yielded a comb-branched or generation zero (G0) arborescent PBG. Further partial deprotection and grafting cycles led to arborescent PBG of generations G1 to G3. The solvent used in the coupling reaction had a dramatic influence on the yield of graft polymers of generations G1 and above, dimethylsulfoxide being preferable to N,N-dimethylformamide. This grafting onto scheme yielded well-defined (M-w/M(n)1.06), high molecular weight arborescent PBG in a few reaction cycles, with number-average molecular weights and branching functionalities reaching over 10(6) and 290, respectively, for the G3 polymer. -Helix to coiled conformation transitions were observed from N,N-dimethylformamide to dimethyl sulfoxide solutions, even for the highly branched polymers. (c) 2013 Wiley Periodicals, Inc.