Improved Carbohydrate Recognition in Water with an Electrostatically Enhanced β-Peptide Bundle

Area of Science:

• Biochemistry
• Molecular Biology
• Supramolecular Chemistry

Background:

• Selective molecular recognition of carbohydrates in aqueous solution remains a significant challenge.
• Designing synthetic receptors for saccharides requires precise control over binding interactions.

Purpose of the Study:

• To develop a β-peptide based system for the selective recognition and binding of simple sugars in neutral aqueous solution.
• To investigate the role of electrostatic interactions in enhancing binding affinity.

Main Methods:

• Structure-guided computational redesign of a β-peptide foldamer.
• Synthesis and characterization of the modified β-peptide 'borono-bundle'.
• Affinity measurements using techniques like Isothermal Titration Calorimetry (ITC) in aqueous buffer.

Main Results:

• The redesigned borono-bundle exhibited significantly increased binding affinity for simple sugars compared to previous designs.
• A binding affinity of 663 M⁻¹ was achieved for fructose in neutral water.
• The electrostatic redesign successfully enhanced the molecular recognition capabilities of the peptide system.

Conclusions:

• The study demonstrates a successful strategy for achieving selective sugar binding in water through electrostatic redesign of β-peptides.
• The developed borono-bundle shows potential for applications in selective catalysis and sensing of carbohydrates.
• Future research will focus on leveraging this system for targeted catalytic transformations.