Heterogeneous H-bonding in a foldamer helix

Area of Science:

• Peptide Chemistry
• Structural Biology
• Organic Chemistry

Background:

• Foldamers are peptide mimics with unique structural properties.
• Alpha/gamma-peptides offer novel secondary structures.
• Understanding helical formation in foldamers is key to their applications.

Purpose of the Study:

• To characterize the structure of new alpha/gamma-peptide foldamers.
• To investigate the role of a cyclically constrained gamma-amino acid (residue I) in secondary structure formation.
• To compare the favorability of different hydrogen bonds within the resulting helix.

Main Methods:

• Crystallographic analysis
• 2D Nuclear Magnetic Resonance (NMR) spectroscopy
• Structural characterization of novel foldamer compounds

Main Results:

• The constrained gamma-amino acid residue I promotes a 12/10-helical secondary structure in alpha/gamma-peptides.
• The 12/10-helix contains two distinct types of internal hydrogen bonds.
• A 12-atom hydrogen bond (C═O(i) → H-N(i+3)) is more favorable than a 10-atom hydrogen bond (C═O(i) → H-N(i-1)).

Conclusions:

• The study demonstrates the formation of a 12/10-helical structure in novel alpha/gamma-peptide foldamers.
• It is the first report showing differential favorability between distinct hydrogen bonds within foldamer helices.
• These findings contribute to the understanding of foldamer structural diversity and stability.