Modular Self-Assembling Peptide Platform with a Tunable Thermoresponsiveness via a Single Amino Acid Substitution

The introduction of a stimulus-responsive property is an effective way to increase the applicability of functional materials in the field of nanobiotechnology. Herein, a peptide platform is devised for constructing elastin-like peptide amphiphiles (ELPAs) that exhibit a temperature-responsiveness that can be easily tuned via a single N-terminal amino acid substitution at the final step of peptide synthesis. Due to the modular property of peptides, the platform based on a miniaturized elastin-like peptide (MELP) can be conjugated with various bioactive peptide sequences in diverse macromolecular topologies. First, the MELP platform is coupled with a short linear RGD peptide. The ELPAs of the peptide conjugates exhibit rapid aggregation (coacervation) and retard disaggregation in response to heating and cooling, respectively. Second, the platform is grafted with an α-helical guest peptide in a lariat-type structure, which forms ELPAs that undergo faster disassembly than the ELPAs without the guest peptide in response to temperature increases. Interestingly, the critical temperatures for the thermoresponsive behaviors are commonly dependent on the hydrophobic and aromatic properties of the N-terminal amino acid residues. These results suggest that this peptide platform possesses great potential for use in the development of smart materials in wide-ranging applications related to temperature change.