Synthesis and characterization of poly-L-lysine with controlled low molecular weight

N-Carboxy-(N-epsilon-benzyloxycarbonyl)-L-lysine anhydride (Z-L-lysine NCA) was polymerized in dimethylformamide with triethylamine, diethylamine or hexylamine as initiator, at varying molar ratios of NCA to initiator (M/I ratio). After removal of the protecting Z-group the resulting poly-L-lysine was characterized with H-1 NMR and MALDI TOF MS. Both diethylamine-and hexylamine-initiated polymerization yielded poly-L-lysine in which the initiators were incorporated at the carboxylic end of the polymer. This indicates that the NCA polymerization occurred exclusively via nucleophilic attack of the initiator on the monomer. On the other hand, when triethylamine was used as the initiator, poly-L-lysine was obtained in which no triethylamine-derived end group could be detected by MS. These polymer chains are most likely end-capped with an N-acyl-2,5-dioxopiperazine group at the carboxylic end of the polymer. Incorporation of diethylamine and hexylamine allowed determination of the degree of polymerization (DP) of the obtained polymers by H-1 NMR. The DP depended linearly on the M/I ratio, for both diethylamine and hexylamine, with higher DPs for the diethylamine-initiated poly-L-lysine at equal M/I ratio.