title: Structural analysis of the epitope recognized by a monoclonal antibody directed against tricyclic antidepressants.
abstract: After somatic cell fusion between splenocytes of immunized BALB/c mice and NS-1 myeloma cells, a clone was obtained that secreted an anti-nortriptyline antibody of the IgG1 kappa isotype. The association constant of this antibody for pharmacologically active tricyclic antidepressant drugs ranged from 0.6 X 10(7) to 3 X 10(7) M-1. From thermodynamic and binding studies as well as tridimensional structures of tested compounds, the epitope recognized by the monoclonal antibody appeared to include both a hydrophobic tricycle in which the two phenyl rings form an angle of 120 to 130 degrees, and a side chain in which the amino group is separated from the two lateral rings of the tricyclic structure by a distance of approximately 5.9 A and 7.5 A, respectively. This conformation seems to be the one interacting with muscarinic acetylcholine brain receptors.
authors.forename: S
authors.initials: S
authors.lastname: Marullo
authors.forename: J
authors.initials: J
authors.lastname: Hoebeke
authors.forename: J G
authors.initials: JG
authors.lastname: Guillet
authors.forename: A D
authors.initials: AD
authors.lastname: Strosberg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D000937:Antigen-Antibody Reactions; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D000939:Epitopes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009661:Nortriptyline / Q000276:immunology*; D011976:Receptors, Muscarinic; D013816:Thermodynamics
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D011976:Receptors, Muscarinic; D009661:Nortriptyline