Bifunctional Peptide–Polymer Conjugate-Based Fibers via a One-Pot Tandem Disulfide Reduction Coupled to a Thio-Bromo “Click” Reaction

Abstract

In view of the potential applications of fibers in material sciences and biomedicine, an effective synthetic strategy is described to construct peptide-based bifunctional polymeric conjugates for supramolecular self-association in solution. A direct coupling method of an α-acyl-brominated peptide Phe-Phe-Phe-Phe (FFFF) with a disulfide-bridged polymeric scaffold of poly(ethylene glycol) (PEG) ( M n,GPC = 8700 g mol –1 , Đ = 2.02) is reported to readily prepare the bi-headed conjugate FFFF-PEG-FFFF ( M n,GPC = 3800 g mol –1 , Đ = 1.10) via a one-pot, tandem disulfide reduction (based on tris(2-carboxyethyl)phosphine hydrochloride (TCEP)) coupled to a thio-bromo “click” reaction. The conjugate was investigated via transmission electron microscopy to exploit supramolecular fibril formation and solvent-dependent structuring into macroscale fibers via fibril–fibril interactions and interfibril cross-linking-induced bundling. Circular dichroism spectroscopic analysis is further performed to investigate β-sheet motifs in such fibrous scaffolds. Overall, this synthetic approach opens an attractive approach for a simplified synthesis of PEG-containing peptide conjugates.

Secondary Structures in Synthetic Poly(Amino Acids): Homo‐ and Copolymers of Poly(Aib), Poly(Glu), and Poly(Asp)

“…These hybrid molecules contain repetitive units of amino acids (oligo( Bn Asp, Bn Glu, [48,49] or Lysine [50,51] )) as middle segments, purely geometrical constraints [52][53][54][55] including artificial 𝛽-turns, [56][57][58] photoswitchable units [59][60][61] or amyloidogenic peptide-sequences. [62][63][64] They are interrupted by "synthetic" intermissions, basically representing -((CH 2 ) n -units of a precise chain length (n = 16-20).…”

“…These hybrid molecules contain repetitive units of amino acids (oligo( Bn Asp, Bn Glu, [ 48,49 ] or Lysine [ 50,51 ] )) as middle segments, purely geometrical constraints [ 52–55 ] including artificial β ‐turns, [ 56–58 ] photoswitchable units [ 59–61 ] or amyloidogenic peptide‐sequences. [ 62–64 ] They are interrupted by “synthetic” intermissions, basically representing –((CH 2 ) n ‐units of a precise chain length ( n = 16–20). To introduce an additional level of complexity and to “break” helices by design, we also studied the achiral amino acid Aib, able to form 3 10 ‐helices to study molecular chirality transfer between different chains as a model for refolding processes.…”

Thioether-based ROS responsive polymers for biomedical applications

“…Their further supramolecular self-assembly led to fibers formation with an average diameter of ∼10 nm, through π–π stacking of aromatic constituents forming β-sheets. 62 Recently, Battaglia and co-workers carried out the one-pot synthesis of oxidation-sensitive supramolecular micelles and vesicles by polymerization-induced self-assembly (PISA) of the N -carboxyanhydride (NCA) precursor of methionine using poly(ethylene oxide) as a stabilizing and hydrophilic block in dimethyl sulfoxide (DMSO). Different morphologies ranging from spherical to wormlike micelles up to vesicles could be obtained by adjusting the hydrophobic block length and concentration.…”

Amphiphilic mPEG-Modified Oligo-Phenylalanine Nanoparticles Chemoenzymatically Synthesized via Papain

“…PEGylation can improve the water solubility and stability of peptides in vivo administration and reduction of immunogenity . PEGylated peptides are able to self-assemble to form various superstructures like nanotubes, micelles, fibrils, and organogels. − In recent years, peptide nanoparticles (NPs) derived from amino acid-based precursors have been attracting interest in the fields of biomedicine and nanobiotechnology. − Peptide building blocks, such as cyclic peptides, aromatic dipeptides, surfactant-like oligopeptides, and cationic dipeptides, display a promising potential in the development of peptide nanoparticles. Various methods of hydrolysis, crosslinking, and solvent exchange have been used for the preparation of peptide nanoparticles.…”