Aziridine-2-carboxylic acid-containing peptides: application to solution- and solid-phase convergent site-selective...

Area of Science:

• Organic Chemistry
• Bioconjugation Chemistry
• Peptide Chemistry

Background:

• Peptide modification is crucial for developing new therapeutics and diagnostics.
• Site-specific conjugation methods are needed for precise control over biomolecule structure and function.
• Nonproteinogenic amino acids offer unique chemical handles for bioconjugation.

Purpose of the Study:

• To develop a method for site- and stereoselective peptide modification.
• To utilize aziridine-2-carboxylic acid for controlled peptide conjugation.
• To enable rapid synthesis of complex thioglycoconjugates.

Main Methods:

• Solid-phase peptide synthesis (SPPS) for incorporating aziridine-2-carboxylic acid.
• Utilizing the electrophilic nature of the aziridine residue for conjugation.
• Employing native chemical ligation for convergent synthesis.

Main Results:

• A robust SPPS methodology for aziridine-containing peptides was established.
• Site-selective conjugation with various thiol nucleophiles (carbohydrates, farnesyl thiol, tags) was achieved.
• Convergent synthesis of complex thioglycoconjugates was demonstrated.

Conclusions:

• Aziridine-2-carboxylic acid serves as an effective tool for site-selective peptide modification.
• The developed method provides rapid access to diverse thioglycoconjugates.
• This strategy holds potential for applications in drug discovery and chemical biology.