Rout Debasish, Sharma Shweta, Agarwala Pratibha, Upadhyaya Arun K, Sharma Akanksha, Sasmal Dibyendu K
Department of Chemistry, Indian Institute of Technology, Jodhpur, Rajasthan 342037, India.
ACS Omega. 2023 Jan 10;8(3):3114-3128. doi: 10.1021/acsomega.2c06447. eCollection 2023 Jan 24.
The interaction between the plasma protein bovine serum albumin (BSA) and the drug ibuprofen (IBU) has been investigated at three different pH values (7.4, 6.5, and 8.0) in the presence of oligosaccharides and surfactants. The interaction analysis of BSA with oligosaccharides and surfactants has also been studied in the absence of the drug ibuprofen. The results obtained give convenient and efficient access to understand the mechanism of binding of ibuprofen to BSA, and the major forces involved are found to be hydrophobic forces, hydrogen bonding and ionic interactions. In addition to that, the formation of inclusion complexes of ibuprofen with oligosaccharides (β-CD and 2-HP-β-CD) has been observed, which has depicted that due to the hydrophobic nature of ibuprofen, it becomes more soluble in the presence of oligosaccharides, but due to the larger size of the inclusion complexes, these could not be able to access the hydrophobic pocket of BSA where tryptophan-212 (Trp-212) resides. The binding interaction between BSA and ibuprofen is observed in the presence of surfactants (SDS and CTAB), which partially unfold the protein. Non-radiative fluorescence resonance energy transfer (FRET) from Trp and Tyr residues of BSA in the presence of an anionic surfactant SDS to ibuprofen has depicted that there is a possibility of drug binding even in the partially unfolded state of BSA protein. Furthermore, the distance between the protein and the drug has been calculated from the FRET efficiency, which gives a comprehensive overview of ibuprofen binding to BSA even in its partially denatured state. The hydrophobic drug binding to the partially unfolded serum albumin protein (BSA) supports the "necklace and bead structures" model and opens up a new direction of drug loading and delivery system, which will have critical therapeutic applications in the efficient delivery of pharmacologically prominent drugs.
在存在寡糖和表面活性剂的情况下，于三种不同的pH值（7.4、6.5和8.0）下研究了血浆蛋白牛血清白蛋白（BSA）与药物布洛芬（IBU）之间的相互作用。在不存在药物布洛芬的情况下，也研究了BSA与寡糖和表面活性剂的相互作用分析。所获得的结果为理解布洛芬与BSA的结合机制提供了便捷有效的途径，并且发现主要作用力为疏水作用力、氢键和离子相互作用。除此之外，还观察到布洛芬与寡糖（β-环糊精和2-羟丙基-β-环糊精）形成了包合物，这表明由于布洛芬的疏水性，它在寡糖存在下变得更易溶解，但由于包合物尺寸较大，它们无法进入色氨酸-212（Trp-212）所在的BSA疏水口袋。在存在表面活性剂（十二烷基硫酸钠和十六烷基三甲基溴化铵）的情况下观察到了BSA与布洛芬之间的结合相互作用，表面活性剂会使蛋白质部分展开。在阴离子表面活性剂十二烷基硫酸钠存在下，从BSA的色氨酸和酪氨酸残基到布洛芬的非辐射荧光共振能量转移（FRET）表明，即使在BSA蛋白部分展开的状态下也有可能发生药物结合。此外，已根据FRET效率计算出蛋白质与药物之间的距离，这为布洛芬即使在其部分变性状态下与BSA的结合提供了全面的概述。疏水性药物与部分展开的血清白蛋白蛋白（BSA）的结合支持了“项链和珠子结构”模型，并开辟了药物负载和递送系统的新方向，这将在药理学上重要药物的高效递送中具有关键的治疗应用。
