Synthesis and ring-opening (Co)polymerization of L-lysine N-carboxyanhydrides containing labile side-chain protective groups

This contribution describes the synthesis and ring-opening (co)polymerization of several L-lysine N-carboxyanhydrides (NCAs) that contain labile protective groups at the ε-NH2 position. Four of the following L-lysine NCAs were investigated: Nε-trifluoroacetyl-L-lysine N-carboxyanhydride, Nε-(tert-butoxycarbonyl)-L-lysine N-carboxyanhydride, Nε-(9-fluorenylmethoxycarbonyl)-L-lysine N-carboxyanhydride, and Nε-nitroveratryloxycarbonyl)-L-lysine N-carboxyanhydride. In contrast to the harsh conditions that are required for acidolysis of benzyl carbamate moieties, which are usually used to protect the ε-NH2 position of L-lysine during NCA polymerization, the protective groups of the L-lysine NCAs presented here can be removed under mildly acidic or basic conditions or by photolysis. As a consequence, these monomers may allow access to novel peptide hybrid materials that cannot be prepared from ε-benzyloxycar-bonyl-L-lysine N-carboxyanhydride (Z-Lys NCA) because of side reactions that accompany the removal of the Z groups. By copolymerization of these L-lysine NCAs with labile protective groups, either with each other or with γ-benzyl-L-glutamate N-carboxyanhydride or Z-Lys NCA, orthogonally side-chain-protected copolypeptides with number-average degrees of polymerization ≤20 were obtained. Such copolypeptides, which contain different side-chain protective groups that can be removed independently, are interesting for the synthesis of complex polypeptide architectures or can be used as scaffolds for the preparation of synthetic antigens or protein mimetics. © 2003 Wiley Periodicals, Inc.