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Molecular modeling application on hapten epitope prediction: an enantioselective immunoassay for ofloxacin optical isomers.
- Source :
-
Journal of agricultural and food chemistry [J Agric Food Chem] 2014 Aug 06; Vol. 62 (31), pp. 7804-12. Date of Electronic Publication: 2014 Jul 29. - Publication Year :
- 2014
-
Abstract
- To deepen our understanding of the physiochemical principles that govern hapten-antibody recognition, ofloxacin enantiomers were chosen as a model for epitope prediction of small molecules. In this study, two monoclonal antibodies (mAbs) mAb-WR1 and mAb-MS1 were raised against R-ofloxacin and S-ofloxacin, respectively. The enantioselective mAbs have a high sensitivity and specificity, and the enantioselectivity is not affected by heterologous coating format reactions. The epitopes of the ofloxacin isomers were predicted using the hologram quantitative structure-activity relationship (HQSAR) and comparative molecular field analysis (CoMFA) approaches. The results consistently show that the epitope of the chiral hapten should be primarily composed of the oxazine ring and the piperazinyl ring and mAbs recognize the hapten from the side of this moiety. The enantioselectivity of mAbs is most likely due to the steric hindrance caused by the stereogenic center of the epitope. Modeling of chiral hapten-protein mimics reveals that ofloxacin isomers remain upright on the surface of the carrier protein. Suggestions to improve the enantioselectivity of antibodies against ofloxacin isomers were also proposed. This study provided a simple, efficient, and general method for predicting the epitopes of small molecules via molecular modeling. The epitope predictions for small molecules may create a theoretical guide for hapten design.
- Subjects :
- Animals
Anti-Bacterial Agents
Antibody Specificity
Epitopes immunology
Female
Haptens immunology
Isomerism
Levofloxacin analysis
Mice
Mice, Inbred BALB C
Models, Molecular
Molecular Structure
Ofloxacin analysis
Ofloxacin chemistry
Quantitative Structure-Activity Relationship
Stereoisomerism
Antibodies, Monoclonal immunology
Epitopes chemistry
Haptens chemistry
Immunoassay methods
Levofloxacin immunology
Ofloxacin immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1520-5118
- Volume :
- 62
- Issue :
- 31
- Database :
- MEDLINE
- Journal :
- Journal of agricultural and food chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 25069865
- Full Text :
- https://doi.org/10.1021/jf404449n