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scFv single chain antibody variable fragment as inverse agonist of the β(2) -adrenergic receptor

Item Type:Article
Title:scFv single chain antibody variable fragment as inverse agonist of the β(2) -adrenergic receptor
Creators Name:Peter, J.C. and Eftekhari, P. and Billiald, P. and Wallukat, G. and Hoebeke, J.
Abstract:Antibodies directed against the second extracellular loop of G protein-coupled receptors were shown to possess functional activities. Using a functional monoclonal antibody against the human {beta}2-adrenergic receptor, a scFv fragment with high affinity for the target epitope was constructed and produced. The fragment recognized the {beta} 2-adrenergic receptors on A431 cells, blocked cAMP accumulation induced by the {beta}2-agonist salbutamol, and decreased basal cAMP accumulation in the same cells. Their in vitro activity was tested on neonatal rat cardiomyocytes. The antibody fragments blocked the chronotropic activity induced by the {beta}2-agonist clenbuterol. They also decreased the in vivo heart beating frequency of mice pretreated with bisoprolol (a {beta}1-adrenergic receptor antagonist) for 4 min after injection. The immunological approach presented here may serve as a strategy for the synthesis of a new class of allosteric modulators for G protein-coupled receptors.
Keywords:Albuterol, Amino Acid Sequence, Amino Acid Sequence Homology, Base Sequence, Beta-2 Adrenergic Receptors, Cultured Cells, Clenbuterol, Cyclic AMP, Drug Dose-Response Relationship, Genetic Models, Immunoglobulin Variable Region, Immunohistochemistry, Inbred BALB C Mice, Kinetics, Molecular Models, Molecular Sequence Data, Monoclonal Antibodies, Myocardium, Peptides, Polyacrylamide Gel Electrophoresis, Tertiary Protein Structure, Time Factors, Tumor Cell Line, Western Blotting, Animals, Mice, Rats
Source:Journal of Biological Chemistry
Publisher:American Society for Biochemistry and Molecular Biology
Page Range:36740-36747
Date:19 September 2003
Official Publication:https://doi.org/10.1074/jbc.M306877200
PubMed:View item in PubMed

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