All along their life cycle, proteins undergo various transformations that can alter their functions while keeping a good part of their primary sequence intact. These multiplication of PTM patterns, alternative splicing forms or products of proteolitic processing cannot be simply resolved with a bottom-up approach, as very few peptides are specific from the given proteoform. However, the information relative to the distribution of different proteoforms is encoded in their intact masse. Being able to catch this information efficiently will drive the biologist into a new analytical dimension, far beyond the traditional gel-based approaches.

Bruker has an history with the analysis of intact proteins, whatever it is with NMR, X-ray Crystallography, Infrared or MS, accessing all structural information, from the primary to the quaternary structure.  Bruker’s UHR ESI-Q-TOF systems are now capable of  delivering accurate mass and isotopic pattern information for hundreds of protein in a mixture within minutes. In the exemple we present,  the combination of dynamic range, broadband transmission and sensitvity makes it possible to resolve several hundreds of proteins from a E.Coli and yeast Lysates in less than 20 minutes. The Dissect™ and SNAP™ algorithms enable to extract the information of co-eluting proteins and retrieve the monoisotopic mass from any isotopically resolved protein, therefore enabling to reveal the proteoforms distribution patterns. First insights in the quantitative capabilities of the approach will be illustrated.