兽药小分子与生物识别元件相互作用研究进展

因不合理或违规使用兽药, 导致兽药原型或代谢物在动物源性食品和水体中残留, 继而危害人类健康、破坏生态环境。因此, 兽药残留快速检测方法的建立显得尤为重要。受体、抗体、适配体等生物识别元件具有分子识别能力, 根据其特性已发开了不同的检测方法, 如免疫分析法、受体检测法及生物传感器法等方法, 广泛用于生物医药的研究。由于分子识别元件是分析的主体, 影响分析的选择性, 因此不同识别元件与兽药相互作用的机制越来越受到人们的重视。随着计算机技术的发展, 同源建模和分子对接广泛用于残留检测技术, 主要用于药物与蛋白质之间、抗原与抗体之间、受体与配体之间等生物分子之间相互作用的研究。笔者重点介绍了单链抗体(ScFv)、受体和适配体3种识别元件与兽药小分子之间的互作机制, 主要分析生物识别元件与兽药结合部位形成的氢键、疏水性及关键氨基酸或碱基, 在分子水平上探究药物与识别元件的机理和规律, 从而找出影响识别元件与药物结合的关键因素, 并对3种识别元件进行了总结, 以期为全面了解识别机制和体外进化, 制备出亲和力更广的ScFv、受体、适配体提供理论支撑, 为后续药物残留检测技术和药物开发奠定基础。

Research Progress on the Interaction Between Small Molecules of Veterinary Drugs and Biometric Elements

At present, due to unreasonable or illegal use of veterinary drugs, their prototypes or metabolites remain in animal derived food and water, which will endanger human health and damage the ecological environment.Therefore, the establishment of rapid detection methods of veterinary drug residues is particularly important.Receptors, antibodies, aptamers and other biometric elements have molecular recognition ability.According to its characteristics, different detection methods have been developed such as immunoassay, receptor detection and biosensor method, which are widely used in biomedical research.Because molecular recognition elements are the main body of analysis and affect the selectivity of analysis, the mechanism of interaction between different recognition elements and veterinary drugs has been paid more and more attention.With the development of computer technology, homologous modeling and molecular docking are widely used in residue detection, mainly used in the study of the interactions between drugs and proteins, antigens and antibodies, receptors and ligands and other biomolecules.This paper focused on the interaction mechanism between three recognition elements of single chain variable fragment (ScFv), receptor and aptamer and veterinary drug small molecules.It mainly analyzed the hydrogen bonds, hydrophobicity and key amino acids or bases formed at the binding site of biometric elements and veterinary drugs.The mechanism and law of drug and recognition element were explored at molecular level, so as to find out the key factors affecting the combination of drug and recognition element, and three recognition elements were summarized, in order to provide theoretical support for the comprehensive understanding of recognition mechanism and in vitro evolution, and prepare ScFv, receptors and aptamers with wider affinity, and lay a foundation for subsequent drug residue detection technology and drug development.