Cover Picture: Proteomics 10'10

Double‐barreled drug delivery? The functional description of human galectin‐3 (hGal‐3) makes me think of something like a monkey, able to hang by its tail and throw rotten or ripe fruit with both hands. In actual fact, the tail of recombinant hGal‐3 has an affinity for β‐galactosides and can direct its multimerization and eventually the crosslinking of cells through their surface glycoconjugates in the presence of a carbohydrate ligand. The “hands” are two sites that bind drug‐like molecules: one binds hydrophobic porphyrins (ZnTPPS4) similar to photosensitizers used for photodynamic therapy, the other binds bohemine, a cyclin dependent anti‐cancer drug. The number and specificity of binding sites was determined by classical methods: fluorescence peak shift, ligand/competitor titration, UV absorbance spectroscopy, and circular dichroism. The old dogs still have some life in them. Bogoeva, V., Proteomics 2010, 10 , 1946–1953. “One of these cells is not like the other ones…” If you are under the age of 50, I'm sure you played that game as you watched Sesame Street or your national equivalent. Cilia or flagella, Gram positive or negative – you know the drill. Here, Mehaffy et al. are looking at bacterial matches from a different perspective, a proteomic distinction point of view. The question is “Can strains of Mycobacterium tuberculosis (TB) be distinguished on the basis of secreted or cytosolic proteomes?” Although minimally variant genetically, TB is phenotypically quite variable. Here the power of iTRAQ has been combined with 2‐DE and MS/MS to look quantitatively at secreted (101 proteins) and cytosolic (137 proteins) proteomes from similar and quite different TB strains. They report 28 proteins were common to both cytosol and secreted fractions. Curiously, an unusual fraction of unknown function proteins carried much of the variability. The more to study…. Mehaffy, C. et al ., Proteomics 2010, 10 , 1966–1984. Targeting the targets Identification of the direct target(s) of a kinase is somewhat akin to finding one particular penguin in a flock of thousands – there is a difference between individuals, but how do they screen (or perhaps scream) through all of the possible mates in a finite time? Here, Morandell et al. approach the flock of kinase targets using tools from chemical genetics, immunochemistry, phospho‐proteomics and quantitative proteomics to assemble a bundle named “QIK”. QIKs capabilities are demonstrated on samples with or without Mek 1 kinase substrates Erk 1 and Erk 2. After examining over 500 additional peptides, the conclusion is that the only phosphopeptides that change in a quantitative fashion with the addition of Mek 1 are Erk 1 and 2. Morandell, S. et al ., Proteomics 2010, 10 , 2015–2025.