Stepwise triple-click functionalization of synthetic peptides

Area of Science:

• Chemical Biology
• Organic Chemistry
• Biochemistry

Background:

• Peptides are increasingly used as molecular scaffolds in biomedicine.
• Developing efficient methods for peptide modification is crucial for their application.
• Current methods may lack efficiency or versatility for complex modifications.

Purpose of the Study:

• To develop an optimized protocol for multi-functionalization of synthetic peptides.
• To enable the creation of complex peptide-based probes and constructs.
• To expand the available methods for postsynthetic peptide modification.

Main Methods:

• Utilized a sequence of Copper(I)-catalyzed Azide-Alkyne Cycloaddition (CuAAC) click reactions.
• Incorporated selective deprotection steps for controlled functionalization.
• Applied the methodology to synthesize heteroglycopeptides and fluorophore-quencher probes.

Main Results:

• Achieved efficient multi-functionalization of synthetic peptides.
• Successfully constructed defined heteroglycopeptides.
• Developed fluorophore-quencher-containing probes for protease activity.
• Demonstrated the versatility of the click chemistry approach.

Conclusions:

• The developed protocol offers an efficient route for postsynthetic peptide modification.
• The methodology expands the capabilities for creating functional peptide-based molecules.
• Commercial availability of azide probes enhances the broad applicability of this technique.