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Monoclonal Antibodies with High Affinity for Spiroperidol
Author(s) -
Luedtke Robert R.,
Korner Mira,
Neve Kim A.,
Molinoff Perry B.
Publication year - 1988
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1988.tb10602.x
Subject(s) - hapten , immunogen , chemistry , antibody , monoclonal antibody , stereochemistry , biochemistry , microbiology and biotechnology , biology , immunology
A diverse panel of monoclonal antibodies was obtained from BALB/c mice immunized with two haptens structurally related to spiroperidol (SPD). Bromoacetyl derivatives of aminospiroperidol (NH 2 SPD) and N ‐amino‐phenethylspiroperidol (NAPS) were synthesized to couple the haptens covalently to a protein carrier for immunization, thereby maintaining the butyrophenone portion of the immunogen. Hybridomas were selected based on their ability to secrete antibody that binds [ 3 H]SPD with high affinity. Equilibrium dissociation constants for these antibodies ranged from 0.2 to > 100 n M . The antigen binding sites of the anti‐NH 2 SPD and anti‐NAPS antibodies were characterized in studies of the inhibition of the binding of [ 3 H]‐SPD by a series of ligands that are either (a) structurally related to SPD or (b) structurally unrelated to the butyrophenones but known to be selective antagonists of the D2 subtype of dopamine receptor. Based on the patterns of inhibition of the binding of [ 3 H]SPD by these compounds, 12 classes of antibody combining sites were identified. Most of these antibodies bound butyrophenones with high affinity. One anti‐NH 2 SPD and four anti‐NAPS antibodies also bound domperidone, a nonbutyrophenone that has a high affinity for D2 receptors. None of the antibodies bound clebopride or sulpiride, D2‐selective antagonists of the benzamide class, or the agonist dopamine.