title: Glycan-Mediated, Ligand-Controlled Click Chemistry for Drug-Target Identification.
abstract: Membrane-bound proteins are important pharmaceutical drug targets, yet few strategies exist for the identification of small-molecule-targeted membrane proteins in live-cell systems. By exploiting metabolic glycan engineering of cell membrane proteins, we have developed an in situ glycan-mediated ligand-controlled click ("GLiCo-Click") chemistry methodology that enables the attachment of small-molecule chemical probes to their receptor protein through glycans on live cells. In addition to enabling receptor enrichment from cell lysates, this strategy can be used to demonstrate target receptor engagement and enables the molecular characterization of receptors.
authors.affiliation: Discovery Chemistry and Technology, Oncology Discovery, Integrated Sciences and Technology, AbbVie Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA. henning.stoeckmann@abbvie.com.
authors.forename: Henning
authors.initials: H
authors.lastname: Stöckmann
authors.affiliation: Discovery Chemistry and Technology, Oncology Discovery, Integrated Sciences and Technology, AbbVie Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA.
authors.forename: Violeta L
authors.initials: VL
authors.lastname: Marin
authors.affiliation: Discovery Chemistry and Technology, Oncology Discovery, Integrated Sciences and Technology, AbbVie Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Nimmer
authors.affiliation: Discovery Chemistry and Technology, Oncology Discovery, Integrated Sciences and Technology, AbbVie Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA.
authors.forename: Corina M
authors.initials: CM
authors.lastname: Balut
authors.affiliation: Discovery Chemistry and Technology, Oncology Discovery, Integrated Sciences and Technology, AbbVie Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Davidson
authors.affiliation: Discovery Chemistry and Technology, Oncology Discovery, Integrated Sciences and Technology, AbbVie Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Richardson
authors.affiliation: Discovery Chemistry and Technology, Oncology Discovery, Integrated Sciences and Technology, AbbVie Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA.
authors.forename: Anil
authors.initials: A
authors.lastname: Vasudevan
mesh_terms: D000595:Amino Acid Sequence; D000954:Antigens, Surface / Q000737:chemistry; D002853:Chromatography, Liquid; D057930:Click Chemistry; D016503:Drug Delivery Systems; D005434:Flow Cytometry; D008024:Ligands; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011134:Polysaccharides / Q000737:chemistry*
chemical_list: D000954:Antigens, Surface; D008024:Ligands; D011134:Polysaccharides