(541e) The Monkey King: A Personal View of the Long Journey Towards a Proteomic Nirvana

The review covers about fifty years of progress in “proteome” analysis, starting from primitive two-dimensional (2D) maps attempts in the early sixties of last century. The polar star in 2D mapping arose in 1975 with the classical paper by O’Farrell in J Biol. Chem. It became the compass for all proteome navigators. Perfection only came, though, with the introduction of immobilized pH gradients, which fixed the polypeptides spots in the 2D plane. Great impulse in proteome analysis came by introducing informatics tools and creating databases, among which Swiss Prot remains the site of excellence. Towards the end of the nineties, 2D chromatography, epitomized by coupling strong cation exchangers with C₁₈ resins, began to be a serious challenge to electrophoretic 2D mapping, although up to the present both techniques are still much in vogue and appear to give complementary results. Yet the migration of “proteomics” into the third millennium was only made possible by mass spectrometry (MS), which today represents the standard analytical tool in any lab dealing with proteomic analysis. Another major improvement has been the introduction of combinatorial peptide ligand libraries (CPLL), which, when properly used, enhance the visibility of low-abundance species by 3 to 4 orders of magnitude. Coupling MS to CPLLs permits to explore at least 8 orders of magnitude in dynamic range on any proteome.