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Kinetic Template-Guided Tethering of Fragments

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Abstract

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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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