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 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.
Highlights
Sulfonamides are widely used to control a number of diseases in the animal industry and aquaculture, as well as for animal growth-promotion [1]
fluorescence polarization immunoassay (FPIA) is based on the degree of movement of the observed emission intensity from the vertical to the horizontal plane, which is related to the mobility of the fluorescently labeled molecule
The introduction of the methoxyl group in the pyrimidine ring at position 4 decreased the binding affinity as seen with sulfameter. This may be due to the effects of other fields like electrostatic, hydrophobic or hydrogen-bonding that may play an important role in the interactions of the sulfonamide analogs and the MAbSMR
Summary
Sulfonamides are widely used to control a number of diseases in the animal industry and aquaculture, as well as for animal growth-promotion [1]. A method that can provide useful information about the topological properties of a hapten can be very useful in helping produce an antibody with the desired affinity and specificity. Efforts have been made to correlate the affinity of antibodies to conformational and electronic properties of a hapten, as previously demonstrated with sulfonamides by using molecular modeling methods [8,11]. A three-dimensional quantitative structure-activity relationship (3D-QSAR) model is developed using comparative molecular field analysis (CoMFA) or comparative molecular similarity indices analysis (CoMSIA). The 3D-QSAR analysis techniques, CoMFA and CoMSIA, were used to describe the quantitative binding affinities of the sulfonamides with the MAbSMR. The Connolly surface of sulfamerazine (hapten), which exhibited the lowest binding affinity to the MAbSMR, was compared with the structures of two sulfonamide analogs. This work may develop knowledge of interactions that govern sulfonamide-antibody binding, and may help in the design of novel, performance enhanced antibodies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
