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 α-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.