Submitted to: Nature Precedings
Publication Type: Proceedings
Publication Acceptance Date: 11/14/2008
Publication Date: 12/12/2008
Citation: Wang, Z., Cao, X., Kai, Z., Beier, R.C., Wu, C., Jiang, H., Cheng, L., Shen, J., Yang, X. 2008. Three dimensional quantitative structure-activity relationships of sulfonamides binding monoclonal antibody by comparative molecular field analysis. Nature Precedings. Available from Nature Precedings <http://hdl.handle.net/10101/npre.2008.2646.1>. 2008. Interpretive Summary: A computer generated model (comparative molecular field analysis) of the binding site of an antibody to 15 sulfonamide drugs was developed. 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 sulfonamide chemicals, were explored. The model has very good predictive ability to determine how unknown sulfonamides would potentially bind the antibody. This 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: The three-dimensional quantitative structure-activity relationship (3D-QSAR) model of sulfonamide analogs, binding a monoclonal antibody (MabSMR) produced against sulfamerazine was carried out by comparative molecular field analysis (CoMFA). The affinities of MabSMR, expressed as Log10IC50, for 17 sulfonamide analogs were determined by competitive fluorescence polarization immunoassay (FPIA). Removal of two outliers from the initial set of 17 sulfonamide analogs improved the predictability of the models. The 3D-QSAR model of 15 sulfonamides resulted in q**2cv values of 0.600, and r**2 values of 0.995, respectively. This novel study combining FPIA with CoMFA 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, which may result in new antibodies with properties already optimized by an antibody-based immunoassay.