title: Multisite-directed inhibitors of protein kinase CK2: new challenges.
abstract: New 4,5,6,7-tetrabromo benzotriazole derivatives have been synthesized, and their activities against CK2 have been tested. A click chemistry approach based on the copper-catalyzed azide-alkyne cycloaddition has been utilized to connect benzotriazoles, which efficiently interact with the ATP-binding site, to other subunits designed to simultaneously bind to the active and the substrate-binding sites of the enzyme. Docking studies allowed us to identify key interactions between CK2 and the designed ligands, which will be useful to optimize this series of multisite-directed inhibitors.
authors.affiliation: Departamento de Química, Facultad de Farmacia, Universidad San Pablo CEU, Urbanización Montepríncipe, 28668 Boadilla del Monte (Madrid), Spain.
authors.forename: Robert
authors.initials: R
authors.lastname: Świder
authors.forename: Maciej
authors.initials: M
authors.lastname: Masłyk
authors.forename: Sonsoles
authors.initials: S
authors.lastname: Martín-Santamaría
authors.forename: Ana
authors.initials: A
authors.lastname: Ramos
authors.forename: Beatriz
authors.initials: B
authors.lastname: de Pascual-Teresa
mesh_terms: D001665:Binding Sites; D047390:Casein Kinase II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D047428:Protein Kinase Inhibitors; D047390:Casein Kinase II