A novel modification of poly(L-lysine) leading to a soluble cationic polymer with reduced toxicity and with potential as a transfection agent

Chemical modification of poly(L-lysine) by hydrogen transfer addition of N,N-dimethylacrylamide to the primary amino groups results in new water soluble derivatives with reduced cell toxicity which maintain basic properties. Kinetic studies on the addition reaction were performed using model compounds, and a reliable kinetic model was obtained which proved to be valuable also in the case of poly(L-lysine). A peculiar feature of the addition reaction of poly(L-lysine) on N,N-dimethylacrylamide is that, starting from partially protonated poly(L-lysine), the reaction stops after that all the unprotonated units originally present have reacted. Toxicological studies on modified poly(L-lysine) in comparsion with parent poly(L-lysine) showed that the modifying reaction leads to a reduction in toxicity.