Peptide and Protein Desulfurization with Diboron Reagents

Area of Science:

• Chemical Synthesis
• Biochemistry
• Organic Chemistry

Background:

• Sulfur-containing compounds are crucial in biological systems.
• Efficient methods for desulfurization are needed for peptide and protein synthesis.
• Existing methods may lack robustness or broad substrate compatibility.

Purpose of the Study:

• To develop a direct and robust desulfurization method.
• To demonstrate the method's compatibility with diverse sulfur-containing biomolecules.
• To integrate the method into existing peptide synthesis workflows.

Main Methods:

• Utilized tris(2-carboxyethyl)phosphine hydrochloride (TCEP) as a water-soluble phosphine.
• Employed tetrahydroxydiboron (B2(OH)4) as a radical initiator.
• Optimized reaction conditions to minimize byproducts and performed desulfurization post-native chemical ligation (NCL) in one pot.

Main Results:

• Achieved direct and robust desulfurization across various substrates.
• Demonstrated compatibility with cysteine residues, alkyl thiols, disulfides, and selenocysteine.
• Successfully minimized oxidized and borylated byproducts through optimized conditions.

Conclusions:

• The developed desulfurization method offers a streamlined approach for complex peptide and protein synthesis.
• The reaction's robustness and broad substrate scope represent a significant advancement.
• This method enhances synthetic strategies by enabling efficient sulfur removal in a single pot after NCL.