Sharifi Maryam, Ezzati Nazhad Dolatabadi Jafar, Fathi Farzaneh, Zakariazadeh Mostafa, Barzegar Abolfazl, Rashidi Mohammad, Tajalli Habib, Rashidi Mohammad-Reza
Research Institute for Applied Physics and Astronomy, University of Tabriz, Tabriz, Iran.
Research Center for Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
Bioimpacts. 2017;7(2):91-97. doi: 10.15171/bi.2017.12. Epub 2017 Jun 7.
The interactions between biomacromolecules such as serum albumin (SA) and various drugs have attracted increasing research attention in recent years. However, the study of SA with those drugs that have relatively high hydrophilicity and a lower affinity for SA could be a challenging issue. At the present study, the interaction of bovine SA (BSA) with neomycin as a hydrophilic drug has been investigated using surface plasmon resonance (SPR) and molecular docking methods. BSA was immobilized on the carboxymethyl dextran hydrogel sensor chip after activation of carboxylic groups through NHS/EDC and, then, the neomycin interaction with BSA at different concentrations (1-128 µM) was investigated. Dose-response sensorgrams of BSA upon increasing concentration of neomycin has been shown through SPR analysis. The small K value (4.96 e at 40°C) demonstrated high affinity of neomycin to BSA. Thermodynamic parameters were calculated through van't Hoff equation at 4 different temperatures. The results showed that neomycin interacts with BSA via Van der Waals interactions and hydrogen bonds and increase of K with temperature rising indicated that the binding process was entropy driven. Molecular docking study confirmed that hydrogen bond was the major intermolecular force stabilizing neomycin-BSA complex. The attained results showed that neomycin molecules can efficiently distribute within the body after interaction with BSA in spite of having hydrophilic properties. Besides, SPR can be considered as a useful instrument for study of the interaction of hydrophilic drugs with SA.
近年来，血清白蛋白（SA）等生物大分子与各种药物之间的相互作用引起了越来越多的研究关注。然而，研究SA与那些亲水性相对较高且与SA亲和力较低的药物可能是一个具有挑战性的问题。在本研究中，使用表面等离子体共振（SPR）和分子对接方法研究了牛血清白蛋白（BSA）与作为亲水性药物的新霉素之间的相互作用。通过NHS/EDC活化羧基后，将BSA固定在羧甲基葡聚糖水凝胶传感器芯片上，然后研究不同浓度（1-128μM）的新霉素与BSA的相互作用。通过SPR分析显示了随着新霉素浓度增加BSA的剂量响应传感图。小的K值（40°C时为4.96 e）表明新霉素对BSA具有高亲和力。在4个不同温度下通过范特霍夫方程计算热力学参数。结果表明，新霉素通过范德华相互作用和氢键与BSA相互作用，并且随着温度升高K值增加表明结合过程是熵驱动的。分子对接研究证实氢键是稳定新霉素-BSA复合物的主要分子间作用力。获得的结果表明，尽管新霉素具有亲水性，但与BSA相互作用后，新霉素分子仍可在体内有效分布。此外，SPR可被认为是研究亲水性药物与SA相互作用的有用工具。
