Highly Branched Poly(l-lysine)

Abstract

This paper describes the synthesis of several novel water-soluble highly branched polypeptides. The synthesis starts with the ring-opening polymerization of epsilon-benzyloxycarbonyl-l-lysine N-carboxyanhydride (Z-Lys NCA) or epsilon-trifluoroacetyl-l-lysine N-carboxyanhydride (TFA-Lys NCA), followed by end functionalization of the peptide chain with N(alpha),N(epsilon)-di(9-fluorenylmethoxycarbonyl)-l-lysine (N(alpha),N(epsilon)-diFmoc Lys). Deprotection of the N(alpha),N(epsilon)-diFmoc Lys end group affords two new primary amine groups that can initiate the polymerization of a second generation of branches. Repetition of this ring-opening polymerization-end functionalization sequence affords highly branched poly(epsilon-benzyloxycarbonyl-l-lysine) (poly(Z-Lys)) and poly(epsilon-trifluoroacetyl-l-lysine) (poly(TFA-Lys)) in a small number of straightforward synthetic steps. Removal of the side-chain protective groups yields water-soluble and highly branched poly(l-lysine)s, which may be of potential interest for a variety of medical applications.