Thio-Bromo “Click” Reaction Derived Polymer–Peptide Conjugates for Their Self-Assembled Fibrillar Nanostructures

Abstract

The synthesis and self-assembly of peptide–polymer conjugates into fibrillar nanostructures are reported, based on the amyloidogenic peptide KLVFF. A strategy for rational synthesis of polymer–peptide conjugates is documented via tethering of the amyloidogenic peptide segment LVFF (Aβ17-20) and its modified derivative FFFF to the hydrophilic poly(ethylene glycol) monomethyl ether (mPEG) polymer via thio-bromo based “click” chemistry. The resultant conjugates mPEG-LVFF-OMe and mPEG-FFFF-OMe are purified via preparative gel permeation chromatography technique (with a yield of 61% and 64%, respectively), and are successfully characterized via combination of spectroscopic and chromatographic methods, including electrospray ionization time-of-flight mass spectrometry. The peptide-guided self-assembling behavior of the as-constructed amphiphilic supramolecular materials is further investigated via transmission electron microscopic and circular dichroism spectroscopic analysis, exhibiting fibrillar nanostructure formation in binary aqueous solution mixture.