Metal affinity capture tandem mass spectrometry for the selective detection of phosphopeptides

Anal Chem. 2006 Sep 1;78(17):6065-73. doi: 10.1021/ac060509y.

Abstract

We report a new method called metal affinity capture that when coupled with tandem mass spectrometry (MAC-MSMS) allows for the selective detection and identification of phosphopeptides in complex mixtures. Phosphopeptides are captured as ternary complexes with Ga(III) or Fe(III) and N(alpha),N(alpha)-bis(carboxymethyl)lysine (LysNTA) in solution and electrosprayed as doubly or triply charged positive ions. The gas-phase complexes uniformly dissociate to produce a common (LysNTA + H)+ ion that is used as a specific marker in precursor ion scans. The advantages of MAC-MSMS over the current methods of phosphopeptide detection are as follows. (1) MAC-MSMS uses metal complexes that self-assemble in solution at pH <5, which is favorable for the production of positive ions by electrospray. (2) Phosphorylation at tyrosine, serine, and threonine is detected by MAC-MSMS. (3) The phosphopeptide peaks in the mass spectra are encoded with the 69Ga-71Ga isotope pattern for selective recognition in mixtures. Detection by MAC-MSMS of singly and multiply phosphorylated peptides in tryptic digests is demonstrated at low-nanomolar protein concentrations.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Esters / chemistry
  • Ions / chemistry
  • Metals / chemistry*
  • Molecular Structure
  • Phosphopeptides / analysis*
  • Phosphopeptides / chemistry*
  • Solutions
  • Tandem Mass Spectrometry / methods*

Substances

  • Esters
  • Ions
  • Metals
  • Phosphopeptides
  • Solutions