Insight into the cross-linking of synthetic polypeptide gels prepared by ring-opening polymerization using l-cystine N-carboxyanhydride

Abstract

Synthetic polypeptides have promising potential for various biomedical applications that often require a cross-linked network for stability against solvents or mechanical stress. Due to the natural occurrence and availability of the l-cystine α-amino acid, l-cystine N-carboxyanhydride (NCA) is commonly used as a cross-linker in the ring-opening (co)polymerization of α-amino acid NCAs to prepare covalently cross-linked synthetic polypeptides. In this work, we show that the l-cystine NCA tends to undergo undesired decomposition side reactions, i.e., β-elimination and formation of 2,5-diketopiperazine, which reduce the amount of the cross-linker available and make it difficult to control the final properties of the materials prepared from it. By using the analogous l-homocystine NCA instead, the decomposition side reactions can be completely avoided. We demonstrate the cross-linking performance of l-cystine NCA compared to l-homocystine NCA by studying the corresponding gels prepared by copolymerization with γ-benzyl-l-glutamate NCA.