Iminoboronate-Based Peptide Cyclization That Responds to pH, Oxidation, and Small Molecule Modulators

Area of Science:

• Chemical Biology
• Organic Chemistry
• Medicinal Chemistry

Background:

• Peptide natural products often feature cyclic scaffolds to enhance target binding affinity.
• Synthetic cyclic peptides are valuable as biological probes and potential therapeutics.
• Developing efficient and versatile peptide cyclization strategies remains a key challenge.

Purpose of the Study:

• To introduce a novel strategy for peptide cyclization.
• To demonstrate the formation of monocyclic and bicyclic peptides using this method.
• To highlight the stimuli-responsive and reversible nature of the cyclization.

Main Methods:

• Intramolecular iminoboronate formation for spontaneous peptide cyclization.
• Utilizing physiological conditions for the cyclization process.
• Investigating the reversibility of the iminoboronate-based cyclization in response to pH, oxidation, and small molecules.

Main Results:

• Successful synthesis of monocyclic and bicyclic peptides via iminoboronate formation.
• Demonstration of spontaneous cyclization under physiological conditions.
• Confirmation of rapid and reversible cyclization triggered by pH, oxidation, and small molecules.

Conclusions:

• A novel and versatile iminoboronate-based strategy for peptide cyclization has been developed.
• This method enables spontaneous formation of cyclic peptides under physiological conditions.
• The stimuli-responsive and reversible nature of this cyclization opens new avenues in chemical biology and drug discovery.