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Title: Investigation of antigen-antibody interactions of sulfonamides with a monoclonal antibody in a fluorescence polarization immunoassay using 3D-QSAR models

item WANG, ZHANHUI - China Agricultural University
item KAI, ZHENPENG - China Agricultural University
item Beier, Ross
item SHEN, JIANZHONG - China Agricultural University
item YANG, XINLING - China Agricultural University

Submitted to: International Journal of Molecular Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/14/2012
Publication Date: 5/23/2012
Citation: Wang, Z., Kai, Z., Beier, R.C., Shen, J., Yang, X. 2012. Investigation of antigen-antibody interactions of sulfonamides with a monoclonal antibody in a fluorescence polarization immunoassay using 3D-QSAR models. International Journal of Molecular Sciences. 13:6334-6351.

Interpretive Summary: A computer-generated model was developed of the binding site of an antibody to 15 sulfonamide drugs aided by using data from a fluorescence polarization study. Antibodies are substances that are produced by the immune system in response to foreign substances or antigens which enter the body. The binding contributions due to different structural features of the sulfonamides were explored. The model has very good predictive ability to determine how unknown sulfonamides would potentially bind the antibody. The model may also be used to help generate new antibodies with better overall binding capabilities with a large group of sulfonamide drugs. This novel study demonstrates that multidisciplinary research can be used as a useful tool to investigate antigen-antibody interactions and provide information required for design of novel haptens. Haptens are used as an antigen during the development of an antibody.

Technical Abstract: A three-dimensional quantitative structure-activity relationship (3D-QSAR) model of sulfonamide analogs binding a monoclonal antibody (MAbSMR) produced against sulfamerazine was carried out by Distance Comparison (DISCOtech), comparative molecular field analysis (CoMFA), and comparative molecular similarity indices analysis (CoMSIA). The affinities of the MAbSMR, expressed as Log10IC50, for 17 sulfonamide analogs were determined by competitive fluorescence polarization immunoassay (FPIA). The results demonstrated that the proposed pharmacophore model containing two hydrogen-bond acceptors, two hydrogen-bond donors, and two hydrophobic centers characterized the structural features of the sulfonamides necessary for MAbSMR binding. Removal of two outliers from the initial set of 17 sulfonamide analogs improved the predictability of the models. The 3D-QSAR models of 15 sulfonamides based on CoMFA and CoMSIA resulted in q2cv values of 0.600 and 0.523 and r2 values of 0.995 and 0.994, respectively, which indicates that both methods have significant predictive capability. Connolly surface analysis, which mainly focused on steric force fields, was performed to complement the results from CoMFA and CoMSIA. This novel study combining FPIA with pharmacophore modeling demonstrates that multidisciplinary research is useful for investigating antigen-antibody interactions and also may provide information required for the design of new haptens.