ISSN:
1573-904X
Keywords:
monoclonal antibodies (MAbs)
;
stereoselectivity
;
specificity
;
5-HTIA agonist
;
molecular lipophilicity potential (MLP)
;
virtual log P
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract Purpose. An immunoconjugate model was proposed to produce stereo-selective 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 Köhler 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 108 to 2.8 X 109 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 mono-hydroxylated metabolites suggest that the lipophilicity behavior could be a valuable tool for predicting Ab-crossreactivity.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1018832810105
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