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Birds of a tether: A tethering strategy for the site-directed discovery of low-molecular-weight fragments that bind weakly to defined protein surfaces is described. A solvent-exposed protein thiol captures acrylamide-modified fragments in a conjugate addition reaction that requires a template to produce a measureable quantity of protein-fragment adduct, which can be rapidly identified by mass spectrometry.
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Nonoo et al. (2012) studied this question.
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