Multilayered Magnetic Nanoparticles as a Support in Solid-Phase Peptide Synthesis
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The synthesis of multilayered magnetic nanoparticles (MNPs) for use as a support in solid-phase peptide synthesis (SPPS) is described. Silanization of magnetite (Fe3O4) nanoparticles with 3-(trimethoxysilyl)propyl methacrylate introduced polymerizable groups on the surface. Polymerization with allylamine, trimethylolpropane trimethacrylate, and trimethylolpropane ethoxylate (14/3 EO/OH) triacrylate provided a polymeric coating and amino groups to serve as starting points for the synthesis. After coupling of an internal reference amino acid and a cleavable linker, the coated MNPs were applied as the solid phase during synthesis of Leu-enkephalinamide and acyl carrier protein (65-74) by Fmoc chemistry. A “high-load” version of the MNP support (0.32 mmol/g) was prepared by four consecutive cycles of Fmoc-Lys(Fmoc)-OH coupling and Fmoc deprotection. Successful synthesis of Leu-enkephalin was demonstrated on the “high-load” MNPs. Chemical stability studies proved the particles to be stable under SPPS conditions and magnetization measurements showed that the magnetic properties of the particles were maintained throughout derivatizations and SPPS. The MNPs were further characterized by high-resolution transmission electron microscopy, inductively coupled plasma atomic emission spectrometry, elemental analysis, and nitrogen gas adsorption measurements.
KeywordsMagnetic materials Nanocomposites Magnetite Multilayer structure Polymer Solid-phase peptide synthesis Support
We thank Dr. Ian Snowball at the Department of Geology, Lund University, for help with magnetic analyses, Ms. Birgitta Lindén at the Department of Chemical Engineering, Lund University, for porosimetry analyses, Dr. Jakob Wagner at the National Center for High Resolution Electron Microscopy, Lund University, for TEM, and Mr. Tommy Olsson, Department of Ecology, Lund University, for ICP-AES. This work was supported by the Swedish Research Council and the Swedish Foundation for Strategic Research (INGVAR, Individual Grant for the Advancement of Research Leaders).
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