TY - JOUR
T1 - Substructure-activity relationship studies on antibody recognition for phenylurea compounds using competitive immunoassay and computational chemistry
AU - Zhang, Fuyuan
AU - Liu, Bing
AU - Liu, Guozhen
AU - Zhang, Yan
AU - Wang, Junping
AU - Wang, Shuo
N1 - Copyright the Author(s) 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.
PY - 2018/2/15
Y1 - 2018/2/15
N2 - 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 μg/L to 42.71 μg/L. All 6 phenylurea herbicides contain a common moiety and three different substitutes. To understand how these three different chemical groups affect the antibody-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 der Waals (vdW) surface of the substituents played a critical role in the antibody-phenylurea recognition process.
AB - 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 μg/L to 42.71 μg/L. All 6 phenylurea herbicides contain a common moiety and three different substitutes. To understand how these three different chemical groups affect the antibody-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 der Waals (vdW) surface of the substituents played a critical role in the antibody-phenylurea recognition process.
UR - http://www.scopus.com/inward/record.url?scp=85042237089&partnerID=8YFLogxK
U2 - 10.1038/s41598-018-21394-x
DO - 10.1038/s41598-018-21394-x
M3 - Article
C2 - 29449597
AN - SCOPUS:85042237089
VL - 8
SP - 1
EP - 8
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 3131
ER -