Solid-Phase Peptide Macrocyclization and Multifunctionalization via Dipyrrin Construction.

Area of Science:

• Organic Chemistry
• Biochemistry
• Materials Science

Background:

• Cyclic peptides offer unique structural and functional properties.
• Developing efficient synthetic routes for complex cyclopeptides remains a challenge.
• Multifunctional linkers are crucial for expanding cyclopeptide applications.

Purpose of the Study:

• To introduce a novel and efficient solid-phase synthesis of multifunctional fluorescent cyclopeptides.
• To explore the versatility of dipyrrin construction for creating diverse cyclic peptide architectures.
• To demonstrate the utility of dipyrrin-containing cyclopeptides as bioimaging probes and sensors.

Main Methods:

• Solid-phase peptide synthesis with dipyrrin construction for macrocyclization.
• Formation of various bicyclic peptides through dipyrrin crosslinking and double-ring formation.
• Transformation of dipyrrin to BODIPY for fluorescence and application as a cancer imaging probe.
• Direct use of dipyrrin as a metal sensor in aqueous media.

Main Results:

• A highly efficient synthetic protocol for multifunctional fluorescent cyclopeptides was established.
• The method accommodates all proteinogenic amino acids and various ring sizes.
• Bicyclic peptides were successfully synthesized, demonstrating the flexibility of dipyrrin-based crosslinking.
• Dipyrrin-containing cyclopeptides showed promise as cancer-selective imaging agents and selective metal sensors.

Conclusions:

• This work significantly advances the peptide macrocyclization toolbox.
• The developed method provides a blueprint for designing multifunctional dipyrrin linkers in cyclopeptides.
• These cyclopeptides hold great potential for diverse bioapplications, including targeted imaging and sensing.