Magnetic nanoparticle-based solid phase peptide synthesis and the synchronous detection of their biological activity

The solid-phase peptide synthesis (SPPS) strategy, as the main procedure of peptide manufacturing, has a profound impact on the research of peptides. The rapid development of nanotechnology is expected to promote the evolution of the solid phase to miniaturization, convenience and multi-function. In this work, silica-coated magnetic ferriferous oxide (Fe3O4) nanoparticles (MNP/SiO2) were used as new generation of solid phase for SPPS in Fmoc chemistry. The superparamagnetic solid phase facilitated a multi-step synthesis reaction due to its magnetic maneuverability, which could efficiently separate reaction intermediates, and were then redispersed in the next-step synthetic solution for peptide elongation. In addition, this strategy further allowed the simultaneous acquisition of magnetic nanoparticle–peptide conjugates as available bioprobes to examine the biological function of synthesized peptides. The feasibility of this novel magnetic nanoparticle-based solid phase peptide synthesis (MNP-SPPS) strategy was confirmed by the synthesis of arginine-glycine-aspartic acid-glycine-glycine (RGDGG) as a model pentapeptide. The simultaneously acquired magnetic nanoparticle–peptide conjugates (RGDGG-MNP/SiO2), possessing excellent biological functions, could be recognized and further internalized by tumor cells through receptor-mediated endocytosis, thereby achieving the extraction and removal of malignant cells in vitro under an external magnetic field. The RGDGG-MNP/SiO2 could further be used as a contrasting agent for tumor-targeting T2 magnetic resonance imaging in vivo. This study developed a novel MNP-SPPS strategy that could realize the simple synthesis of peptides, and the synchronously obtained nanoprobes could quickly detect the biological activity of the target synthetic sequence. This strategy may have broad application prospects in combinatorial chemistry and the construction of peptide libraries in the future.