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

Liquid-phase peptide synthesis (LPPS) continues to evolve toward more sustainable and efficient methodologies. In this study, we introduce Cyclover as a tag that enables efficient, tunable LPPS in 2Me-THF using propylphosphonic anhydride (T3P®) as a coupling reagent. The extraction protocol reduces the PMI ∼2.7-fold while maintaining high purity and isolated yield, offering a greener and versatile route to complex peptides.