title: Efficient and facile synthesis of acrylamide libraries for protein-guided tethering.
abstract: A kinetic template-guided tethering (KTGT) strategy has been developed for the site-directed discovery of fragments that bind to defined protein surfaces, where acrylamide-modified fragments can be irreversibly captured in a protein-templated conjugate addition reaction. Herein, an efficient and facile method is reported for the preparation of acrylamide libraries from a diverse range of amine fragments using a solid-supported quaternary amine base.
authors.affiliation: Global Discovery Chemistry, Novartis Horsham Research Centre , Wimblehurst Road, Horsham RH12 5AB, U.K.
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Allen
authors.forename: Peter R
authors.initials: PR
authors.lastname: Curran
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Brearley
authors.forename: Valerie
authors.initials: V
authors.lastname: Boissel
authors.forename: Lilya
authors.initials: L
authors.lastname: Sviridenko
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Press
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Stonehouse
authors.forename: Alan
authors.initials: A
authors.lastname: Armstrong
mesh_terms: D020106:Acrylamide / Q000138:chemical synthesis* / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D015394:Molecular Structure; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000588:Amines; D011804:Quinolines; D020106:Acrylamide; C487932:neratinib