Production and characterization of 22 monoclonal antibodies directed against S 20499, a new potent 5-HT1A chiral agonist: influence of the hapten structure on specificity and stereorecognition

Got, P.; Raimbaud, E.; Bussey, C.; Caron, Giulia; Carrupt, Pierre-Alain; Walther, B.; Bensussan, A.; Scherrmann, J. M.

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Title		Production and characterization of 22 monoclonal antibodies directed against S 20499, a new potent 5-HT1A chiral agonist: influence of the hapten structure on specificity and stereorecognition
Authors		Got, P. Raimbaud, E. Bussey, C. Caron, Giulia Carrupt, Pierre-Alain Walther, B. Bensussan, A. Scherrmann, J. M.
Published in		Pharmaceutical Research. 1999, vol. 16, no. 5, p. 725-735
Abstract		PURPOSE: An immunoconjugate model was proposed to produce stereoselective monoclonal antibodies (MAbs) for the quantitation of a 5-HT1A agonist, S 20499. MAbs produced were characterized in terms of stereoselectivity and specificity towards the opposite enantiomer and structural analogs. METHODS: The immunogen was formed following the effective addition of a butanoic acid spacer arm between the parent S 20499 structure and bovine serum albumin (BSA). After fusion (modified Kohler and Milstein's procedure), specificity of MAbs was obtained using the Abraham's criteria. Experimental and calculated partition coefficients were determined. RESULTS: Twenty-two hybridoma cell lines were established secreting MAbs (apparent association constants ranging from 1.1 x 10(8) to 2.8 X 10(9) M(-1)). Several MAbs showed cross-reactivity levels of less than 5% with S 20500 (optical antipode), which could allow a stereospecific assay to be set up. Both chroman and azaspiro moieties were part of the epitopic site. Dealkylation and hydroxylation(s) led to various crossreactivity levels. Four antibody families were described in terms of specificity. CONCLUSIONS: This study highlighted the influence of the immunoconjugate construction (coupling site and type of spacer arm) in the immuno-stereospecificity of Abs. The results obtained for two monohydroxylated metabolites suggest that the lipophilicity behavior could be a valuable tool for predicting Ab-crossreactivity.
Keywords		Animals — Antibodies, Monoclonal/chemistry/immunology — Antibody Specificity — Cross Reactions — Female — Haptens/chemistry/immunology — Hybridomas — Lipids/chemistry/immunology — Mice — Mice, Inbred BALB C — Models, Immunological — Protein Structure, Tertiary — Serotonin Agonists/chemistry/immunology — Spiro Compounds/chemistry/*immunology — Stereoisomerism
Identifiers		PMID: 10350017
Full text		Article - Limited access to UNIGE Other version: http://www.springerlink.com/content/w0l7j8131357764g/fulltext.pdf
Citation (ISO format)		GOT, P. et al. Production and characterization of 22 monoclonal antibodies directed against S 20499, a new potent 5-HT1A chiral agonist: influence of the hapten structure on specificity and stereorecognition. In: Pharmaceutical Research, 1999, vol. 16, n° 5, p. 725-735. https://archive-ouverte.unige.ch/unige:10586