Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 14176-53955, Iran.
Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, 14115-111, Iran.
Enzyme Microb Technol. 2019 Jan;120:117-123. doi: 10.1016/j.enzmictec.2018.10.010. Epub 2018 Oct 23.
Surface plasmon resonance (SPR) biosensor has been utilized for monitoring analyte-ligand interactions in modern drug discovery processes. SPR biosensors measure the change in refractive indexes over the course of analyte molecules' binding to a specific immobilized ligand on sensor chip. This effort highlights a comprehensive SPR study besides enzymatic assay for discovery of new Angiotensin Converting Enzyme (ACE) inhibitors via screening of medicinal plants. At first, five medicinal plants were selected as potential sources for developing new ACE inhibitors through hydrolyzing hippuryl-L-histidyl-L-leucine (HHL) assay. The interaction of selected extracts with immobilized ACE on the sensor chip (500D) confirmed that the Onopordum acanthium L. had the greatest ACE inhibition activity among the set of compounds and its active compound (onopordia) was isolated. SPR biosensor used to evaluate binding affinity of onopordia and ACE. Equilibrium constant (K), and changes in Gibb's free energy of the binding (ΔG) values for the interaction of onopordia with ACE were found to be 10.24 μM and -28.48 kJ/mol, respectively. Computational analysis supported the binding of onopordia to the ACE active site. Kinetic and thermodynamic parameters of binding revealed that onopordia is an acceptable ACE inhibitor and could treat hypertension. SPR biosensor can be used to improve the drug discovery process for many important classes of drug targets due to its great sensitivity.
表面等离子体共振（SPR）生物传感器已被用于监测现代药物发现过程中分析物-配体相互作用。SPR 生物传感器测量分析物分子与传感器芯片上特定固定配体结合过程中折射率的变化。这项工作除了酶分析之外，还突出了对 SPR 的全面研究，通过对药用植物进行筛选，发现新的血管紧张素转化酶（ACE）抑制剂。首先，选择了五种药用植物作为通过水解 hippuryl-L-histidyl-L-leucine (HHL) 测定法开发新型 ACE 抑制剂的潜在来源。所选提取物与固定在传感器芯片（500D）上的 ACE 的相互作用证实，刺苞菊属植物在这组化合物中具有最大的 ACE 抑制活性，其活性化合物（刺苞菊属）被分离出来。SPR 生物传感器用于评估刺苞菊属与 ACE 的结合亲和力。平衡常数（K）和结合吉布斯自由能变化（ΔG）的值分别为 10.24 μM 和-28.48 kJ/mol。计算分析支持刺苞菊属与 ACE 活性位点的结合。结合的动力学和热力学参数表明，刺苞菊属是一种可接受的 ACE 抑制剂，可用于治疗高血压。SPR 生物传感器由于其高灵敏度，可以用于改善许多重要药物靶点的药物发现过程。
