Magnetic decantation-enabled pot- and time-economical liquid-phase peptide synthesis

Soluble support (tag)-assisted liquid-phase peptide synthesis (LPPS) is a greener alternative to solid-phase peptide synthesis (SPPS) because it reduces the consumption of reagents and solvents throughout the synthetic process. In conventional LPPS, tagged peptides are selectively precipitated and isolated by filtration; however, filtration can be time-consuming depending on the physical properties of the precipitate. Herein, we report a magnetic decantation-enabled, filtration-free LPPS protocol using chemically stable and reversibly dispersible hydrophobic magnetic nanoparticles. Magnetic decantation performed after each coupling/deprotection sequence enables pot- and time-economical peptide synthesis without filtration. The feasibility of the protocol was demonstrated through the synthesis of leucine-enkephalin as a model peptide, affording the target peptide in excellent yield and high purity without chromatographic purification.