Substructure-activity relationship studies on antibody recognition for phenylurea compounds using computational chemistry

作者：Zhang, Fuyuan; Liu, Bing; Liu, Guozhen; Zhang, Yan; Wang, Junping; Wang, Shuo^*

来源：Scientific Reports, 2018, 8(1): 3131.

DOI：10.1038/s41598-018-21394-x

• BROAD-SPECIFICITY
• CRYSTAL-STRUCTURE
• IMMUNOASSAY
• HAPTEN
• HERBICIDES
• OFLOXACIN
• EPITOPE
• EXPLANATION
• INHIBITORS
• ALGORITHM

Based on the structural features of fluometuron, an immunizing hapten was synthesized and conjugated to bovine serum albumin as an immunogen to prepare a polyclonal antibody. However, the resultant antibody indicated cross-reactivity with 6 structurally similar phenylurea herbicides, with binding activities (expressed by IC50 values) ranging from 1.67 mu g/L to 42.71 mu g/L. All 6 phenylurea herbicides contain a common moiety and three different substitutes. To understand how these three different chemical groups affect the anti body-phenylurea recognition activity, quantum chemistry, using density function theory (DFT) at the B3LYP/6-311++ G(d,p) level of theory, was employed to optimize all phenylurea structures, followed by determination of the 3D conformations of these molecules, pharmacophore analysis, and molecular electrostatic potential (ESP) analysis. The molecular modeling results confirmed that the geometry configuration, pharmacophore features and electron distribution in the substituents were related to the antibody binding activity. Spearman correlation analysis further elucidated that the geometrical and electrostatic properties on the van derWaals (vdW) surface of the substituents played a critical role in the antibody-phenylurea recognition process.

• 出版日期2018-2-15
• 单位天津科技大学