Hybrid Sequences that Express both Aromatic Amide and α-Peptidic Folding Features

Area of Science:

• Supramolecular Chemistry
• Organic Chemistry
• Polymer Science

Background:

• Foldamers are synthetic oligomers that mimic the folding of proteins.
• Combining aliphatic and aromatic units in foldamers can lead to novel conformational properties.
• Understanding these hybrid structures is key to designing new functional materials.

Purpose of the Study:

• To investigate the solid-state conformations of foldamers containing both alpha-amino acids and quinoline monomers.
• To provide evidence for the combined folding propensities of aliphatic and aromatic main-chain units in foldamers.
• To explore the sequence-dependency of conformation in these hybrid foldamer systems.

Main Methods:

• Synthesis of foldamers with an XQQ repeat motif, where X is an alpha-amino acid and Q is a quinoline-based monomer.
• Crystallization of foldamer compounds from different solvents (water and organic solvents).
• Solid-state structural analysis using X-ray crystallography.

Main Results:

• Foldamers with an XQQ repeat motif adopt conformations influenced by both alpha-amino acid and quinoline components.
• Crystals of a phenylalanine-quinoline foldamer (compound 2) showed an aromatic helix with peptide-like hydrogen bonding.
• Crystals of a serine-quinoline foldamer (compound 3) exhibited a helix-turn-helix structure, with side chains impacting main-chain hydrogen bonding.

Conclusions:

• Hybrid foldamers combining aliphatic (alpha-amino acids) and aromatic (quinoline) units exhibit unique, sequence-dependent conformations.
• These structures demonstrate that aromatic folding features can be incorporated into foldamer designs.
• The findings highlight the potential for creating novel foldamer architectures with combined folding characteristics.