Centre for Advanced Studies, Department of Chemistry, North-Eastern Hill University, Shillong, 793 022, India.
Centre for Advanced Studies, Department of Chemistry, North-Eastern Hill University, Shillong, 793 022, India.
Colloids Surf B Biointerfaces. 2016 Oct 1;146:514-22. doi: 10.1016/j.colsurfb.2016.06.061. Epub 2016 Jun 29.
The interaction and binding behavior of the well-known psychoactive stimulant drugs theophylline (THP) and theobromine (THB) with lysozyme (LYS) was monitored by in-vitro fluorescence titration and molecular docking calculations under physiological condition. The quenching of protein fluorescence on addition of the drugs is due to the formation of protein-drug complex in the ground state in both the cases. However, the binding interaction is almost three orders of magnitude stronger in THP, which involves mostly hydrogen bonding interaction in comparison with THB where hydrophobic binding plays the predominant role. The mechanism of fluorescence quenching (static type) remains same also in presence of gold and silver nanoparticles (NPs); however, the binding capacity of LYS with the drugs changes drastically in comparison with that in aqueous buffer medium. While the binding affinity of LYS to THB increases ca. 100 times in presence of both the NPs, it is seen to decrease drastically (by almost 1000 fold) for THP. This significant modulation in binding behavior indicates that the drug transportation capacity of LYS can be controlled significantly with the formation protein-NP noncovalent assembly system as an efficient delivery channel.
在生理条件下，通过体外荧光滴定和分子对接计算，监测了著名的精神兴奋剂茶碱（THP）和可可碱（THB）与溶菌酶（LYS）的相互作用和结合行为。在这两种情况下，药物的加入导致蛋白质荧光猝灭是由于在基态下形成了蛋白质-药物复合物。然而，与 THB 相比，THP 的结合相互作用要强三个数量级，其中涉及到的主要是氢键相互作用，而 THB 中则主要是疏水结合起作用。在存在金和银纳米粒子（NPs）的情况下，荧光猝灭的机制（静态类型）仍然相同；然而，与在水缓冲介质中相比，LYS 与药物的结合能力发生了剧烈变化。虽然 LYS 与 THB 的结合亲和力在两种纳米粒子存在下增加了约 100 倍，但与 THP 相比，它的结合亲和力急剧下降（几乎下降了 1000 倍）。这种结合行为的显著调节表明，通过形成蛋白质-NP 非共价组装系统作为有效的输送通道，可以显著控制 LYS 的药物输送能力。
