Controlling Peptide Self-Assembly through a Native Chemical Ligation/Desulfurization Strategy

Area of Science:

• Biomaterials Science
• Supramolecular Chemistry
• Peptide Chemistry

Background:

• Peptide self-assembly is a key strategy for creating functional biomaterials.
• Native chemical ligation (NCL) offers a powerful method for peptide synthesis and modification.
• Controlling peptide assembly and disassembly is crucial for advanced material applications.

Purpose of the Study:

• To synthesize self-assembling peptides with maintained chemical diversity using NCL.
• To investigate the formation of self-supporting gels from these modified peptides.
• To explore the disassembly mechanism and rheological properties of the peptide gels.

Main Methods:

• Oxo-ester-mediated NCL reactions to incorporate cysteine and unnatural amino acids (penicillamine).
• Characterization of self-assembled peptide structures using microscopy (helical nanofibers).
• Analysis of self-assembly interactions via FTIR, CD, fluorescence spectroscopy, and MS (ESI).
• Induction of peptide disassembly using desulfurization with TCEP and glutathione at elevated temperatures.

Main Results:

• Successful synthesis of self-assembling peptides incorporating diverse amino acid residues.
• Formation of self-supporting gels composed of helical nanofibers.
• Confirmation of covalent and non-covalent interactions governing self-assembly.
• Demonstration of triggered peptide disassembly by converting Cys to Ala and penicillamine to Val.
• Observation of significant shear-thinning and thixotropic behavior in the gels.

Conclusions:

• NCL/desulfurization strategy enables the creation of chemically diverse self-assembling peptides.
• The resulting peptide gels exhibit tunable structural and rheological properties.
• This approach provides a platform for developing responsive and dynamic peptide-based materials.