The invention provides non-affinity based isotope tagged peptides,
chemistries for making these peptides, and methods for using these
peptides. In one aspect, tags comprise a reactive site (RS) for reacting
with a molecule on a protein to form a stable association with the
peptide (e.g., a covalent bond) and an anchoring site (AS) group for
reversibly or removably anchoring the tag to a solid phase such as a
resin support. Anchoring may be direct or indirect (e.g., through a
linker molecule). Preferably, the anchoring site comprises a biotin
compound. Preferably, the tag comprises a mass-altering label, such as a
stable isotope, such that association of the tag with the peptide can be
monitored by mass spectrometry. The reagents can be used for rapid and
quantitative analysis of proteins or protein function in mixtures of
proteins.