title: Kinetic template-guided tethering of fragments.
abstract: 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.
authors.affiliation: Department of Chemistry, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK.
authors.forename: Rebecca H
authors.initials: RH
authors.lastname: Nonoo
authors.forename: Alan
authors.initials: A
authors.lastname: Armstrong
authors.forename: David J
authors.initials: DJ
authors.lastname: Mann
mesh_terms: D000178:Acrylamides / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D055808:Drug Discovery / Q000379:methods*; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D013058:Mass Spectrometry; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000378:metabolism*; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000178:Acrylamides; D008024:Ligands; D013438:Sulfhydryl Compounds; D013940:Thymidylate Synthase; D005978:Glutathione