Controlled reversible methionine-selective sulfimidation of peptides

Area of Science:

• Chemical Biology
• Organic Chemistry
• Peptide Chemistry

Background:

• Site-selective peptide modification is crucial for understanding peptide structure-function relationships.
• Methionine-selective modification presents significant challenges due to limited available strategies.

Purpose of the Study:

• To develop a general and reversible modification strategy targeting methionine residues in peptides.
• To enable late-stage peptide functionalization and advance peptide-based drug discovery.

Main Methods:

• Ruthenium-catalyzed sulfimidation of peptides to form reversible N═S bonds.
• Traceless cleavage of the N═S bond using glutathione for peptide release.

Main Results:

• Demonstrated a convenient and effective method for methionine-selective peptide modification.
• Successfully applied the strategy to bioactive peptides, peptide stapling, peptide-drug conjugates, and split-and-pool synthesis.

Conclusions:

• The developed on/off strategy via methionine-selective reversible sulfimidation offers a unique tool for peptide chemistry.
• This method facilitates precise peptide manipulation and holds promise for peptide-drug discovery.