Cyclover-Assisted Liquid-Phase Peptide Synthesis Using T3P® as a Green Coupling Reagent

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Biochemistry

Background:

• Liquid-phase peptide synthesis (LPPS) is crucial for producing peptides.
• There is a continuous need for more sustainable and efficient LPPS methods.
• Current methods may face challenges in terms of efficiency, sustainability, and scalability.

Purpose of the Study:

• To introduce Cyclover, a novel tag for enhanced LPPS.
• To demonstrate efficient and tunable peptide synthesis in 2Me-THF.
• To develop a greener extraction protocol for peptide purification.

Main Methods:

• Development and application of the Cyclover tag in LPPS.
• Utilizing propylphosphonic anhydride (T3P®) as the coupling reagent.
• Optimization of an extraction protocol to improve sustainability.

Main Results:

• Cyclover enables efficient and tunable LPPS in 2-methyltetrahydrofuran (2Me-THF).
• The use of T3P® as a coupling reagent proved effective.
• The optimized extraction protocol reduced the Process Mass Intensity (PMI) by approximately 2.7-fold.
• High purity and isolated yields were maintained throughout the process.

Conclusions:

• Cyclover represents a versatile tool for advancing sustainable peptide synthesis.
• The developed method offers a greener and more efficient route for complex peptide production.
• This approach has the potential to significantly impact the field of peptide manufacturing.