Orthogonally reactive amino acids and end groups in NCA polymerization

Functional amino acids whose reactivity is compatible with the polymerization of α-amino acid- N -carboxyanhydrides (NCAs) have received a lot of attention in recent years. The appeal of these reactive monomers lies in the fact that the resulting polymers can be easily modified in one controlled post-polymerization step, leading to a variety of polypeptidic materials like helical non-natural polycations or glycopeptides. This review highlights recent developments in the field and focuses on the different reactive groups like alkynes, alkenes, azides, chlorides and S -alkylsulfonyls. Furthermore, the modifications after polymerization are discussed, pointing out advantages and challenges. Besides orthogonal functionalities in the side chain, different approaches are summarized to modify α- and ω-chain ends with orthogonal functionalities for grafting to and grafting from applications. Thus, new materials can be produced through mild modifications as presented. Finally, we also highlight the development of orthogonally reactive NCAs for the synthesis of polypeptoids, a field that is relatively unexplored, but offers great possibilities for example for polypept(o)idic hybrid materials. We summarize recent strategies for the synthesis of orthogonally reactive polypeptides and polypeptoids by direct and post-polymerization approaches.