Bioorthogonal synthesis of supramolecular peptide polymers

High molecular weight supramolecular peptide polymers with tunable composition, chain flexibility and dynamic properties represent the next-generation advanced materials that overcome the limitations of covalently constructed synthetic polymers. Herein, computationally designed peptides capable of forming antiparallel, coiled-coil, α-helical bundles were utilized as the monomers (bundlemer) to synthesize high molecular weight protein-like supramolecular assemblies. Solution phase step-growth polymerization was performed in aqueous media employing an efficient, rapid and bioorthogonal cycloaddition reaction between s-tetrazines (Tz) and trans-cyclooctenes (TCO). The resultant polymers were characterized physically to determine the intrinsic viscosity, diffusion coefficient and hydrodynamic radius. The apparent polymer molecular weight was estimated to be 100-3000 kDa. Measurements by transmission electron microscope and small angle X-ray scattering indicate the formation of long, semiflexible/flexible rods with a Kuhn length of 6-7 nm. When the polymerization concentration increased, physical gels with defined viscoelastic properties were obtained via intermolecular entanglements. Hydrogels prepared at a higher bundlemer concentration were found stiffer than those obtained at a lower concentration. Overall, the combination of novel coiled-coil bundlemer with bioorthogonal Tz-TCO ligation led to the establishment of protein-like supramolecular polymers.