MOLECULAR MIMICRY OF RECEPTORS FOR ALKALOID DRUGS

长期目标是了解各种生物受体 系统与麻醉性生物碱药物相互作用。 该研究项目旨在 初步了解了 吗啡、尼古丁和相关药物特异性识别和结合 利用现代分子生物学、生物物理测量和 超分子计算化学 实现这一目标的方式是 使用理论和实验分子建模研究， 将使用抗体-配体结合位点作为受体-配体的范例 - 互动。 模拟生物受体位点的抗体， 它们的立体特异性识别和结合配体可以作为一种 模型的研究相互作用的成分的配体和 受体的 使用定量结构-活性配体结合研究， 配体诱导的荧光猝灭，mRNA/cDNA测序技术， 计算机辅助建模和动力学模拟以及X射线晶体学 衍射研究，我们将广泛表征的结合位点， 单克隆抗体（mAb）结合生物碱药物吗啡和 尼古丁。 抗体结合位点已经在许多 调查，但这项研究是第一次使用理论 和实验方法来表征麻醉剂的结合位点 毒品 我们必须了解受体药物的基础 因此，治疗药物滥用和新的 药物可以以合理和预测的方式开发。

The long term objective is to understand how various biological receptor systems interact with narcotic alkaloid drugs. This research project seeks to gain a preliminary insight into the physiochemical rules governing specific recognition and binding of morphine, nicotine and related drugs of abuse using modern molecular biology, biophysical measurements and supramolecular computational chemistry. The objective will be accomplished using theoretical and experimental molecular modelling studies in which we will use antibody-ligand binding sites as a paradigm of receptor-ligand -interactions. Antibodies which mimic biological receptor sites in terms of their stereospecific recognition and binding of ligands can serve as a model for the study of interactive constituents of both the ligand and receptor. Using quantitative structure-activity ligand binding studies, ligand induced fluorescence quenching, mRNA/cDNA sequencing techniques, computer-aided modelling and dynamics simulations and x-ray crystallography diffraction studies, we will extensively characterize the binding sites of monoclonal antibodies (mAb) which bind the alkaloid drugs morphine and nicotine. Antibody binding sites have been examined in numerous investigations, but this study is the first of its kind to use theoretical and experimental approaches to characterize the binding sites for narcotic drugs. It is imperative that we understand the basis of receptor-drug interactions so that strategies in treating drug abuse and new pharmaceuticals may be developed in a rational and predictive manner.