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首页> 外文期刊>Royal Society Open Science >Spectroscopic and molecular docking studies reveal binding characteristics of nazartinib (EGF816) to human serum albumin
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Spectroscopic and molecular docking studies reveal binding characteristics of nazartinib (EGF816) to human serum albumin

机译：光谱和分子对接研究揭示了Nazartinib（EGF816）对人血清白蛋白的结合特征

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The interactions of novel anti-cancer therapeutic agents with the different plasma and tissue components, specifically serum albumins, have lately gained considerable attention due to the significant influence of such interactions on the pharmacokinetics and/or -dynamics of this important class of therapeutics. Nazartinib (EGF 816; NAZ) is a new anti-cancer candidate proposed as a third-generation epidermal growth factor receptor tyrosine kinase inhibitor that is being developed and clinically tested for the management of non-small cell lung cancer. The current study aimed to characterize the interaction between NAZ and human serum albumin (HSA) using experimental and theoretical approaches. Experimental results of fluorescence quenching of HSA induced by NAZ revealed the development of a statically formed complex between NAZ and HSA. Interpretation of the observed fluorescence data using Stern–Volmer, Lineweaver–Burk and double-log formulae resulted in binding constants for HSA-NAZ complex in the range of (2.34–2.81) × 10 4 M –1 over the studied temperatures. These computed values were further used to elucidate thermodynamic attributes of the interaction, which showed that NAZ spontaneously binds to HSA with a postulated electrostatic force-driven interaction. This was further verified by theoretical examination of the NAZ docking on the HSA surface that revealed an HSA-NAZ complex where NAZ is bound to HSA Sudlow site I driven by hydrogen bonding in addition to electrostatic forces in the form of pi-H bond. The HSA binding pocket for NAZ was shown to encompass ARG 257, ARG 222, LYS 199 and GLU 292 with a total binding energy of ?25.59 kJ mol –1 .
机译：新型抗癌治疗剂与不同的血浆和组织成分，特别是血清酶组分的相互作用由于这种相互作用对该重要课程的药代动力学和/或动力学的显着影响，术语最近受到了相当大的关注。 Nazartinib（EGF 816; NAZ）是一种新的抗癌候选者，被提出为第三代表皮生长因子受体酪氨酸激酶抑制剂，用于管理非小细胞肺癌的临床测试。目前的研究旨在使用实验和理论方法表征奈良和人血清白蛋白（HSA）之间的相互作用。纳兹诱导的HSA荧光猝灭的实验结果显示纳兹和HSA之间静态形成的复合物的发展。使用Stern-Volmer，Lineweaver-Burk和双对数公式的观察到的荧光数据的解释导致HSA-NAZ复合物的结合常数在所研究的温度下（2.34-2.81）×10 4m -1的范围内。这些计算值进一步用于阐明相互作用的热力学属性，这表明NAZ与假设的静电力驱动的相互作用自发地结合HSA。通过对揭示HSA-NAZ络合物的HSA-NAZ络合物的理论检查进一步验证，其中纳兹与HSA Sudlow位点I的氢键合的HSA Sudlow位点，除了PI-H键的形式之外。纳兹的HSA绑定口袋被证明是arg 257，arg 222，Lys 199和Glu 292，其总绑定能量为25.59 kJ mol -1。

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