Mass spectrometric analysis of mono- and multi-phosphopeptides by selective binding with NiZnFe₂O₄ magnetic nanoparticles

Nat Commun. 2013:4:1656. doi: 10.1038/ncomms2662.

Abstract

Selective isolation of mono- and multi-phosphorylated peptides is important for understanding how a graded protein kinase or phosphatase signal can precisely modulate the on and off states of signal transduction pathways. Here we report that metal ions at exposed octahedral sites of nano-ferrites, including Fe3O4, NiFe₂O₄, ZnFe₂O₄ and NiZnFe₂O₄, have distinctly selective coordination abilities with mono- and multi- phosphopeptides. Due to their intrinsic magnetic properties and high surface area to volume ratios, these nanoparticles enable the rapid isolation of mono- and multi-phosphopeptides by an external magnetic field. Model phosphoprotein α-casein and two synthesized mono- and di-phosphopeptides have been chosen for proof-of-principle demonstrations, and these nanoparticles have also been applied to phosphoproteome profiling of zebrafish eggs. It is shown that NiZnFe₂O₄ is highly selective for multi-phosphopeptides. In contrast, Fe₃O₄, NiFe₂O₄ and ZnFe₂O₄ can bind with both mono- and multi-phosphopeptides with relatively stronger affinity towards mono-phosphopeptides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Ferric Compounds / chemistry*
  • Magnetics*
  • Metal Nanoparticles*
  • Molecular Sequence Data
  • Nanoparticles / chemistry*
  • Peptides / chemistry*
  • Phosphoproteins / chemistry*
  • Phosphorylation
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods*
  • Zebrafish

Substances

  • Ferric Compounds
  • Peptides
  • Phosphoproteins