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) (Mn,GPC = 8700 g mol-1, Đ = 2.02) is reported to readily prepare the bi-headed conjugate FFFF-PEG-FFFF (Mn,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.