Intrinsically Photoswitchable α/β Peptides toward Two-State Foldamers

Area of Science:

• Peptide Chemistry
• Supramolecular Chemistry
• Organic Synthesis

Background:

• Peptide foldamers are valuable for designing novel biomaterials.
• Controlling foldamer structure and self-assembly is crucial for advanced applications.
• Photoisomerizable units offer a pathway for external control over molecular behavior.

Purpose of the Study:

• To introduce a photoisomerizable β-amino acid into peptide foldamers.
• To investigate the structural and self-association consequences of E-Z photoisomerization.
• To demonstrate reversible control over supramolecular self-assembly in peptide foldamers.

Main Methods:

• One-pot Pd/Cu-catalyzed olefin oxidative amidation for peptide coupling.
• Photochemical E-Z isomerization of the incorporated 3-aminoprop-2-enoic acid residue.
• Crystallographic analysis of model compounds to study structural changes.

Main Results:

• Successful incorporation of (Z)-3-aminoprop-2-enoic acid into peptide foldamers.
• Demonstration of reversible E-Z photoisomerization of the amino acid linkage.
• Crystallographic data revealed distinct 3D structures and self-association patterns for E and Z isomers.
• Reversible switching of supramolecular self-association was achieved by photoisomerization.

Conclusions:

• The photoisomerizable β-amino acid is a versatile building block for peptide foldamers.
• Photochemical control over the unsaturated linkage enables tunable self-assembly.
• This strategy provides a novel method for on/off control of supramolecular structures in foldamers.