Herringbone Helical Foldamers from Aromatic Ether Derived ϵ-Amino Acid Peptides

Area of Science:

• Supramolecular Chemistry
• Peptide Chemistry
• Organic Chemistry

Background:

• Peptides are versatile molecules with diverse structural possibilities.
• Aromatic ether linkages offer unique properties for peptide backbone modification.
• Controlling peptide self-assembly into specific higher-order structures remains a challenge.

Purpose of the Study:

• To investigate the self-assembly of aromatic ether-based epsilon-amino acid peptides.
• To understand the role of hydrogen bonding and pi-pi stacking in helical structure formation.
• To explore the influence of terminal chirality on peptide helical sense and amplification.

Main Methods:

• Synthesis of aromatic ether-derived epsilon-amino acid peptides.
• Structural analysis using techniques like X-ray crystallography or NMR spectroscopy (implied).
• Circular dichroism (CD) spectroscopy to study helical structure and chirality.

Main Results:

• Peptides self-assembled into herringbone helical structures.
• Bifurcated hydrogen bonding (NH-O-NH and O-NH-O) and pi-pi stacking stabilized the helices.
• Diaryl ether bonds facilitated turn motifs and hydrogen bond acceptance.
• Chiral centers at the C-termini induced a single-handed helical screw sense.
• Helical sense amplification was observed with increasing peptide chain length, confirmed by CD spectroscopy.

Conclusions:

• Aromatic ether linkages are effective in directing peptide self-assembly into complex helical structures.
• Hydrogen bonding and pi-pi stacking are crucial for stabilizing the observed herringbone helical motifs.
• Introduction of chirality provides a mechanism for controlling and amplifying helical sense in peptide oligomers.