Polylysines (PL) are highly interesting polymers due to their biocompatibility and their high number of reactive amino groups. So far it was not possible to synthesize them directly from L-lysine. Here, we describe two different synthesis routes to selectively polymerize lysine in one batch without the use of protection groups. Applying 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide as activating agent for the polycondensation Of L-lysine in water gave selectively linear epsilon-PLL. In contrast to this, the polymerization Of L-lysine in chloroform in the presence of dicyclohexyl carbodiimide and 18-crown-6 ether selectively afforded pure alpha-PLL. We also assessed the capability of polylysine derivatization by polymer analog reactions with acetic anhydride, methyl iodide and 2,4,6-trinitrobenzenesulfonic acid. (C) 2008 Wiley Periodicals, Inc.