Helical templating of oligopeptides by cyclodextrin dimers

Area of Science:

• Supramolecular Chemistry
• Chemical Biology
• Biophysical Chemistry

Background:

• Beta-cyclodextrins are cyclic oligosaccharides with a hydrophobic cavity.
• Inducing specific peptide conformations like alpha-helices is crucial for molecular recognition.
• Designing receptors for selective peptide binding and folding remains a challenge.

Purpose of the Study:

• To synthesize and evaluate beta-cyclodextrin-based receptors for inducing helical folds in peptides.
• To investigate the structural requirements for effective receptor-peptide interactions.
• To explore the potential of these receptors in molecular recognition applications.

Main Methods:

• Synthesis of dimeric and monomeric beta-cyclodextrin receptors.
• Circular dichroism (CD) spectroscopy to monitor peptide folding.
• Titration studies using CD and isothermal titration calorimetry (ITC).
• Design of peptides with specific hydrophobic residues (L-p-t-butylphenylalanine and tryptophan).

Main Results:

• A dimeric beta-cyclodextrin receptor derived from a [1,1'-biphenyl]-4,4'-dithiol core selectively induced helical folding in a peptide containing L-p-t-butylphenylalanine.
• Other tested receptors (monomeric and different dimeric structures) did not induce significant helical folding.
• Binding affinity (K(a)) was in the range of 10(4)-10(5) M(-1) for the effective receptor-peptide complex.
• No helical folding was observed with a similar peptide where L-p-t-butylphenylalanine was replaced by tryptophan.

Conclusions:

• Beta-cyclodextrin-based receptors can be designed to induce specific peptide conformations.
• The structure of the receptor core and the nature of the peptide's hydrophobic residues are critical for successful folding.
• These receptors show promise for the molecular recognition of hydrophobic, pre-formed alpha-helical peptides in aqueous environments.