Although mass spectrometry has become a powerful tool for the functional 
analysis of biological systems, complete proteome characterization cannot yet be 
achieved. Instead, the sheer complexity of living organisms demands 
fractionation of cellular extracts to enable more targeted analyses. Here, we 
introduce the concept of "fluorous proteomics," whereby specific peptide subsets 
from samples of biological origin are tagged with perfluorinated moieties and 
subsequently enriched by solid-phase extraction over a fluorous-functionalized 
stationary phase. This approach is extremely selective, yet can readily be 
tailored to enrich different subsets of peptides. Additionally, this methodology 
overcomes many of the limitations of traditional bioaffinity-based enrichment 
strategies, while enabling new affinity enrichment schemes impossible to 
implement with bioaffinity reagents. The potential of this methodology is 
demonstrated by the facile enrichment of peptides bearing particular side-chain 
functionalities or post-translational modifications from tryptic digests of 
individual proteins as well as whole cell lysates.