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

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 q2 cv 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.

通过距离比较（DISCOtech）、比较分子场分析（CoMFA）和比较分子相似性指数分析（CoMSIA），对与抗磺胺甲基嘧啶单克隆抗体（MAbSMR）结合的磺胺类似物建立了三维定量构效关系（3D - QSAR）模型。通过竞争性荧光偏振免疫分析（FPIA）测定了MAbSMR对17种磺胺类似物的亲和力（以Log10IC50表示）。结果表明，所提出的包含两个氢键受体、两个氢键供体和两个疏水中心的药效团模型描述了磺胺类药物与MAbSMR结合所必需的结构特征。从最初的17种磺胺类似物中去除两个异常值提高了模型的预测能力。基于CoMFA和CoMSIA对15种磺胺类药物建立的3D - QSAR模型，其交叉验证q2值分别为0.600和0.523，r2值分别为0.995和0.994，这表明这两种方法都具有显著的预测能力。进行了主要关注立体力场的Connolly表面分析，以补充CoMFA和CoMSIA的结果。这项将FPIA与药效团建模相结合的新研究表明，多学科研究对于研究抗原 - 抗体相互作用是有用的，并且还可能为新半抗原的设计提供所需信息。