A review of the role of chemical modification methods in contemporary mass spectrometry-based proteomics research.

For more than two decades, mass spectrometry has been a central technology for proteomics research. During this time, the use of chemical reactions to introduce tags for quantification, affinity enrichment and other uses has facilitated the comprehensive profiling of the proteome by mass spectrometry in many ways. In the last decade, the introduction of more powerful instruments and more sophisticated data acquisition and data analysis routines has made some strategies obsolete, while making other approaches practically feasible only now. Here, the current status of chemical tagging strategies in proteomics is reviewed, with a particular emphasis on proteome quantification workflows, strategies for the enrichment of (post-translationally) modified proteins and peptides, and methods for structural proteomics.