Top-Down Protein Sequencing
Top-Down sequencing (TDS) extends the analytic possibilities of Bruker mass spectrometers significantly. TDS permits the direct access to sequence information even from large, undigested proteins. It powerfully detects and localizes chemical modifications, PTMs, mutations and protein isoforms that are more difficult to detect using classical trypsin digests.
TDS also provides the ability to characterize protein termini in a targeted fashion and extends capabilities significantly that were previously expected from Edman sequencing.
Common to all TDS methods is the utilization of fragmentation techniques that produce peptide bond fission directly at the site of excitation in the peptide sequence. This provides regular sequence ladders that are relatively simple to interpret. The TDS methods include ISD on the MALDIs, ETD on the spherical ion trap and ECD on the FTMS.