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首页> 外文期刊>Journal of Agricultural and Food Chemistry >Investigation of an Immunoassay with Broad Specificity to Quinolone Drugs by Genetic Algorithm with Linear Assignment of Hypermolecular Alignment of Data Sets and Advanced Quantitative Structure-Activity Relationship Analysis
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Investigation of an Immunoassay with Broad Specificity to Quinolone Drugs by Genetic Algorithm with Linear Assignment of Hypermolecular Alignment of Data Sets and Advanced Quantitative Structure-Activity Relationship Analysis

机译:数据集超分子比对线性分配和高级定量构效关系分析的遗传算法研究对喹诺酮类药物具有广泛特异性的免疫分析方法

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摘要

A polyclonal antibody against the quinolone drug pazufloxacin (PAZ) but with surprisingly broad specificity was raised to simultaneously detect 24 quinolones (QNs). The developed competitive indirect enzyme-linked immunosorbent assay (ciELISA) exhibited limits of detection (LODs) for the 24 QNs ranging from 0.45 to 15.16 ng/mL, below the maximum residue levels (MRLs). To better understand the obtained broad specificity, a genetic algorithm with linear assignment of hypermolecular alignment of data sets (GALAHAD) was used to generate the desired pharmacophore model and superimpose the QNs, and then advanced comparative molecular field analysis (CoMFA) and advanced comparative molecular similarity indices analysis (CoMSIA) models were employed to study the three-dimensional quantitative structure activity relationship (3D QSAR) between QNs and the antibody. It was found that the QNs could interact with the antibody with different binding poses, and cross-reactivity was mainly positively correlated with the bulky substructure containing electronegative atom at the 7-position, while it was negatively associated with the large bulky substructure at the 1-position of QNs.
机译:提出了一种针对喹诺酮药物帕珠沙星(PAZ)但具有令人惊讶的广泛特异性的多克隆抗体,可同时检测24种喹诺酮(QN)。已开发的竞争性间接酶联免疫吸附测定(ciELISA)表现出24个QN的检测限(LOD),范围从0.45至15.16 ng / mL,低于最大残留水平(MRL)。为了更好地理解所获得的广泛特异性,使用遗传算法对数据集的超分子比对进行线性分配(GALAHAD),以生成所需的药效团模型并叠加QN,然后进行高级比较分子场分析(CoMFA)和高级比较分子采用相似性指标分析(CoMSIA)模型研究QN与抗体之间的三维定量结构活性关系(3D QSAR)。发现QNs可以以不同的结合姿势与抗体相互作用,交叉反应性主要与7位含有负电性原子的庞大亚结构呈正相关,而与1位具有较大的大亚结构呈负相关。 QN的位置。

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