洋地黄毒素是一种强心苷,用于治疗心力衰竭和心律失常。然而,其治疗浓度范围很窄。高剂量的洋地黄毒苷与严重的副作用有关;因此,有必要开发可以控制其血浆水平的递送系统。在这种情况下,溶菌酶的结合,一种有许多应用的重要蛋白质,与洋地黄毒苷已被研究,以看到前者作为载体的能力。这些研究是使用实验和计算方法进行的。添加洋地黄毒苷后,溶菌酶的固有荧光增加。荧光结果表明,溶菌酶与洋地黄毒苷之间存在较强的相互作用,主要是,通过疏水力。Further,洋地黄毒苷通过引起溶菌酶的部分解折叠而轻微影响溶菌酶的二级结构。溶菌酶中洋地黄毒苷的优选结合位点是蛋白质的大腔。分子对接研究还确立了疏水性力在结合中的主要作用,并具有氢键的重要支持。还计算并讨论了游离洋地黄毒苷的前沿分子轨道以及与溶菌酶的络合。分子动力学模拟研究的发现阐明,当与洋地黄毒苷结合的溶菌酶复合物的第一和第三构象对比时,第二种构象促进结构稳定性,降低灵活性,并增强溶菌酶的致密性和折叠性能。总体研究表明,溶菌酶可以作为药物制剂中洋地黄毒苷的潜在载体。
Digitoxin is a cardiac glycoside used to treat heart failure and heart arrhythmia. However, its therapeutic concentration range is very narrow. High doses of
digitoxin are associated with severe side effects; therefore, it is necessary to develop the delivery system which can control the plasma levels of it. In this context, the binding of lysozyme, an important protein having many applications, with
digitoxin has been studied to see the ability of the former as a carrier. The studies were carried out using both experimental and computational methods. The intrinsic fluorescence of lysozyme increased on the addition of
digitoxin. Fluorescence results suggested that there was a strong interaction between lysozyme and digitoxin which was favored, mainly, by hydrophobic forces. Further, digitoxin affected the secondary structure of lysozyme slightly by causing the partial unfolding of lysozyme. The preferred binding site of
digitoxin within lysozyme was the large cavity of the protein. Molecular docking studies also established the principal role of hydrophobic forces in the binding with a significant support of hydrogen bonding. Frontier molecular orbitals of free digitoxin and in complexation with lysozyme were also computed and discussed. The findings from molecular dynamics simulation studies elucidate that, when contrasted with the first and third conformations of the digitoxin-bound lysozyme complex, the second conformation promotes structural stability, reduces flexibility, and enhances the compactness and folding properties of lysozyme. The overall study shows that lysozyme could act as a potential carrier for digitoxin in pharmaceutical formulations.