In this issue: Proteomics – Clinical Applications 4/2009

In this issue of Proteomics – Clinical Applications you will find the following highlighted articles: Reverse Phase! Reverse Phase! Enemy kinase dead ahead! “How many molecular torpedoes are fluorescing?” asks the captain. “The new waveguide sensor reports 1000 to 2000, sir.” you reply. “No problemo” the senior officer fires back, “load photodiodes for data point capture.” Don't you wish your experiments were so exciting? No problemo if you are chasing down kinase inhibitors with the chemistry and high sensitivity waveguide optical system described by van Oostrum et al. in this paper. Theoretically capable of detecting as few as 600 fluorescent molecules, a practical limit of 1 to 2000 will do for scanning the spots of the lysate array. Cells are grown, treated experimentally and lysed in 96‐well dishes. Target molecules are detected and quantitated with antibodies or other labeled specific binding species. “All clear, sir!” van Oostrum, J. et al., Proteomics Clin. Appl. 2009, 3 , 412–422. 3,4‐dihydroisoquinolinium: calmodulin tail or dog? Calmodulin is kind of like one of the big dumb guys that “protects” the little boss guy in a gangster movie. He doesn't move unless instructed to, then he can wring your neck as quick as you please or pick you up and dust you off as nice as you please. Jung et al. found 3,4‐dihydroisoquinolinium salt (IHY‐153) during a phage display screen of 1200 small antifungal molecules for those that inhibited the growth of any of a number of cancer cell lines. With a candidate in hand, they gave it the works: titration for activity against four synchronized cell lines, synthesis of biotinylated analogues both active and inactive, phage display panning against expressed human cDNA libraries, surface plasmon resonance analysis of binding kinetics of IHY‐153 to calmodulin (Cam), model docking and more. It all fit together very neatly: IHY‐153 wags Cam. Jung, H. J. et al., Proteomics Clin. Appl. 2009, 3 , 423–432. Correcting colorectal cancer: the role of NSAIDs Colorectal cancer strikes 150 000 US residents a year and kills 50 000 people per year, the third highest rate of cancer deaths for the region. The disease is treatable with non‐steroidal anti‐inflammatory drugs (NSAIDs) when the adenomatous polyps have not begun to spread or show signs of transformation. NSAIDs include aspirin, celecoxib, sulindac and selective cyclooxygenase (COX)‐2 inhibitors. Ji et al. examine the secreted protein products of a colorectal cancer cell line in response to administration of sulindac using optimized sample prep and DIGE analysis methods. They were careful to avoid conditions and times that would be affected by sulindac‐induced apoptosis. Proteins markedly under‐ or over‐expressed were identified by in‐gel digestion and LC‐MS/MS and, in some cases, by Western blots. Proteins of special interest found included Mac‐2BP, ALIX, profilin, 14‐3‐3‐e, IL‐8, GRO, Cab45 and calumenin. Ji, H. et al., Proteomics Clin. Appl. 2009, 3 , 433–451.