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Abstract Stimuli‐responsive peptides, particularly pH‐responsive variants, hold significant promise in biomedical and technological applications by leveraging the broad pH spectrum inherent to biological environments. However, the limited number of natural pH‐responsive amino acids within biologically relevant pH ranges presents challenges for designing rational pH‐responsive peptide assemblies. In our study, we introduce a novel approach by incorporating a library of non‐natural amino acids featuring chemically diverse tertiary amine side chains. Hydrophobic and ionic properties of these non‐natural amino acids facilitate their incorporation into the assembly domain when uncharged, and electrostatic repulsion promotes disassembly under lower pH conditions. Furthermore, we observed a direct relationship between the number of substitutions and the hydrophobicity of these amino acids, influencing their pH‐responsive properties and enabling rational design based on desired transitional pH ranges. The structure‐activity relationship of these pH‐responsive peptides was evaluated by assessing their antimicrobial properties, as their antimicrobial activity is triggered by the disassembly of peptides to release active monomers. This approach not only enhances the specificity and controllability of pH responsiveness but also broadens the scope of peptide materials in biomedical and technological applications.
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Dynamic Response of Surface‐Bound Peptides to a pH Perturbation Under Controlled Electrostatic Conditions
Abstract The dynamic conformations of a thin peptide film covalently‐linked to the surface of a transparent electrode are characterized over the course of a perturbation to their local pH by a photoacid under a controlled electrostatic potential. The local environment at this functionalized electrified interface is probed by the ultrafast fluorescence intensity and transient anisotropy of chromophores sparsely attached to the peptide side chains. A partition of chromophores into two sub‐populations is observed, one buried in the peptide layer and another that is solvent exposed, and their relative contributions to the observed fluorescence signal are affected by both pH and voltage stimuli. The photophysical properties of solvent‐exposed chromophores reveal that while the average conformation of the peptide mat is dictated by the pH of the surrounding electrolyte, their fluctuations are largely determined by the local electrostatic conditions set by the electrode's surface potential.
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- Award ID(s):
- 2123516
- PAR ID:
- 10418928
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Macromolecular Rapid Communications
- Volume:
- 44
- Issue:
- 15
- ISSN:
- 1022-1336
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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