One-shot Synthesis of Peptide Amphiphiles with Applications in Directed Graphenic Assembly.

High molecular weight, synthetic block copolypeptides that self-assemble are in high demand for biomedical applications. The current standard method for synthesis of block copolypeptides is the controlled ring-opening polymerization (ROP) of alpha-amino acid N-carboxyanhydride (NCA) monomers, where block architectures can be created by sequential NCA monomer addition. Recently, researchers have focused on developing reaction conditions and initiation systems that make NCA ROP more convenient, particularly for interdisciplinary labs without designated polypeptide facilities. In an effort to further simplify and increase the convenience of polypeptide synthesis, we developed a one-shot copolymerization strategy that allows access to block copolypeptides by capitalizing on the inherently faster reactivity of NCA monomers, compared to NTA (N-thiocarboxyanhydride) monomers. For the first time, we combine an NCA and NTA monomer in one reaction to kinetically promote block copolypeptide formation, providing a convenient alternative to sequential monomer addition. The controlled nature of this copolymerization technique is supported by a molecular weight that is modulated by the concentration of the initiator and low dispersities. We used this one-shot copolymerization to synthesize p(lysine)-b-p(leucine), a known peptide amphiphile (PA). Our one-shot PAs are antimicrobial and can spontaneously form ordered, micron-scale assemblies. Covalent conjugation of one-shot PAs to a graphenic backbone results in a functional graphenic material (FGM) with a self-assembled morphology, paving the way for creation of sophisticated FGM scaffolds with polypeptide-templated, hierarchical order. Overall, we demonstrate that this novel, one-shot copolymerization strategy produces functional copolypeptides with macroscopic sequence control.