Ortho-Phthalaldehyde (OPA)-based chemoselective protein bioconjugation and peptide cyclization

Area of Science:

• Chemical Biology
• Organic Chemistry
• Biochemistry

Background:

• Native protein and peptide modification are crucial for chemical biology.
• Existing methods often require harsh conditions or protecting groups.
• Developing efficient and mild bioconjugation and cyclization strategies is essential.

Purpose of the Study:

• To develop novel Ortho-Phthalaldehyde (OPA)-based reactions for native protein modification.
• To establish OPA-mediated chemoselective peptide cyclization under aqueous conditions.
• To expand the toolbox for constructing functional peptides and proteins.

Main Methods:

• Utilizing the OPA-amine reaction for native protein biconjugation.
• Employing OPA-alkyne bifunctional linkers for proteome profiling.
• Developing an OPA-amine-thiol three-component reaction for direct peptide cyclization.
• One-pot modification of OPA-guided cyclic peptides with N-maleimide.

Main Results:

• OPA rapidly modifies primary amines in peptides and proteins under physiological conditions.
• OPA-alkyne linkers facilitate proteome profiling applications.
• Chemoselective peptide cyclization is achieved directly on unprotected peptides in aqueous buffer.
• Further functionalization of cyclic peptides is possible in a one-pot procedure.

Conclusions:

• OPA-based reactions provide effective methods for native protein modification and bioconjugation.
• The OPA-amine-thiol reaction enables efficient and direct peptide cyclization.
• These advancements offer versatile strategies for protein engineering and cyclic peptide synthesis.