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

Abstract

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.

The Blanket Effect: How Turning the World Upside Down Reveals the Nature of Graphene Oxide Cytocompatibility

“…GO solid surfaces—such as thin films or pellets—are unstable in water and redisperse, preventing traditional contact angle measurements. [ 66,67 ] The contact angles of the GO dispersions show minor differences compared to DI water (Figure S2F, Supporting Information). For the increasingly oxidized GO materials, contact angle increases with increasing backbone oxidization.…”

“…However, we have previously shown that the DLS‐determined Z‐average diameter reasonably agrees with the particle dimensions measured using high‐resolution optical microscopy, atomic force microscopy, and scanning electron microscopy. [ 66–70 ] Thus, for experimentally relevant micron‐sized sheets of GO, settling will dominate.…”

Self-Assembling Peptides and Carbon Nanomaterials Join Forces for Innovative Biomedical Applications

“…There is growing interest in the conjugation of antimicrobial peptides with antibacterial graphene-based materials [ 180 ], for instance for potential applications in wound healing. To this end, one-pot ring-opening copolymerization of lysine and leucine N -carboxyanhydride into self-assembling polypeptides was used as a simple strategy to yield self-assembling antimicrobials that were also conjugated to graphene to yield hierarchical structures [ 181 ]. Antibacterial membranes were developed by combining a self-assembling palmitoyl tetrapeptide with GO flakes [ 134 ].…”

An Inspection into Multifarious Ways to Synthesize Poly(Amino Acid)s

“…Zhang provided two efficient ways to synthesize polypeptides from 𝛼-amino acid NTAs in DCM, hexane, and heptane. [79,81] In addition to nonpolar and low polar solvents, amine-initiated NTA polymerizations are also reported to be carried out in polar solvents including DMF [102,80] and THF [9] (Scheme 5vii). However, the researches focus on the preparation and application of PAAs while investigation into the polymerization mechanism and controllability is insufficient.…”

“…The polypeptide amphiphiles assembled into various graphemic materials such as micelle, vesicle, and sheet according the composition of polypeptides. [80]…”