Metal labeling for quantitative protein and proteome analysis using inductively-coupled plasma mass spectrometry

Method development for the analytics of biomolecules has an enormous impact on biochemistry, biology, medicine and life sciences. In particular, methods for peptide and protein quantification are required for the study of the proteome of organisms in order to understand fundamental processes of life. Most popular approaches use stable isotope labeling and molecular mass spectrometry (MS).This review highlights recent quantification strategies based on biomolecule labeling with metal tags and inductively-coupled plasma MS (ICP-MS) and their parallel characterization by molecular MS. This new discipline at the interface of analytical chemistry and biochemistry is a rapidly growing research field. It includes the chemical derivatization of functional groups in proteins (e.g., with lanthanide chelates, ferrocenes, organomercury compounds and iodine), and their ultra-sensitive detection and quantification by ICP-MS, so that limits of detection for proteins down to the attomole level have been achieved. Quantification is realized with simple metal standards or stable metal isotopes (isotope-dilution analysis). We critically discuss different approaches and emphasize the prospects of future needs and developments.