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

Abstract

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 lariattype 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.

Sequence isomerism-dependent self-assembly of glycopeptide mimetics with switchable antibiofilm properties

“…Oligopeptides' capability of assembling into stimuli-responsive biomimetic superstructures has attracted great attention due to their interesting applications as biomaterials 1–5. The self-assembled superstructures are able to reversibly respond to external stimuli or environmental changes,6–10 which can be used to mimic soft structures in nature such as protein assemblies 11. A classic molecular model has been developed for constructing oligopeptide superstructures 12–16.…”

Self-Assembling Peptides and Their Application in the Treatment of Diseases

“…They coupled the MELP platform to a short linear RGD peptide and grafted an α-helical guest peptide to the platform in a lariat-type structure. The peptide platform devised by this group provides a new insight into the development of stimuli-responsive materials with wide ranging applications, including temperature-responsive drug delivery and controlled modulation of protein–protein interactions [83].…”

“…Peptide platform based on an miniaturized elastin-like peptide (MELP) for developing elastin-like peptide (ELP) amphiphiles with a thermo-responsive behavior that can be controlled by varying the types of conjugated guest–peptides, macromolecular topologies, and N-terminal amino acid residues. Reprinted with permission from [83]. …”

Peptide–nanoparticle conjugates: a next generation of diagnostic and therapeutic platforms?

“…Their ultra-small size and high surface-area-to-volume ratio are advantageous in the development of engineered materials that can uniquely interact with a variety of nano- and micro-sized biomaterials [12]. The most straightforward approach to fabricate peptides-based nanostructures is self-assembly [13, 14]. However, the spontaneity in the thermodynamic process does not allow the construction of nano-scale constructs having precisely regulated shape, size, and compositions.…”