Traceless protein labeling http://www.nature.com/nchembio/journal/v5/n5/abs/nchembio.157.html http://www.nature.com/nchembio/journal/v5/n5/full/nchembio0509-275.html If this procedure really does work as they say, what a really, really slick idea this group has come up with. Not only does this have the potential to surpass GFP tagging for proteins, you can tune your affinity tags for almost any protein possible so long as you have a ligand for it (without having to do any genetic manipulation). Better yet, you can pick any single probe you wanted to, attach biotin, or almost anything else you could think of. It seems like a fantastic idea. So can someone explain to me why this works? Why don't these traceless affinity tags simply attach to any old nucleophile within the cell? Why must the ligand direct it to the binding pocket of the targeted protein first before it will cleave? Does the hindrance of water prevent it from cleaving until it sees the binding pocket in order to undergo the Sn2 rxn with the nucleophilic protein amino acid residue (binding pocket shields the tosyl from water?)? The western blots they do look absolutely amazing, especially the one from the rat. The "proximity effects" mentioned seemed like a bunch of hand waving for explaining why it works and doesn't randomly attach any nucleophile, but hey if it works, it works.