Squaratides: a tunable platform for anion binding in peptide-inspired macrocycles

Area of Science:

• Supramolecular Chemistry
• Organic Chemistry
• Chemical Biology

Background:

• Peptidomimetic macrocycles are important for molecular recognition.
• Developing novel scaffolds with tunable properties remains a challenge.

Purpose of the Study:

• To introduce a new class of sequence-defined peptidomimetic macrocycles, termed squaratides.
• To investigate the ion-binding capabilities of squaratides for acetate and chloride.
• To explore the role of sidechain functionality in controlling binding affinity and stoichiometry.

Main Methods:

• Synthesis of sequence-defined peptidomimetic macrocycles incorporating squaramide units.
• Design of a tunable peptide backbone.
• Ion-binding studies to assess affinity and stoichiometry with acetate and chloride ions.
• Systematic modification of sidechain functionality.

Main Results:

• Successful synthesis of a new class of macrocycles, squaratides.
• Demonstrated binding of squaratides to acetate and chloride ions.
• Showcased that sidechain functionality can modulate binding affinity and stoichiometry.
• Established the modular nature of the squaratide scaffold.

Conclusions:

• Squaratides represent a novel and versatile class of peptidomimetic macrocycles.
• The squaratide scaffold offers tunable control over ion binding.
• These findings open new avenues for designing receptors for specific anions.