Institute of Physics, Kazan Federal University, 18 Kremlevskaya st., Kazan, 420008, Russia.
Institute of Natural Sciences and Pharmacy, Mari State University, 1 pl. Lenina, Yoshkar-Ola, 424001, Russia.
Biochem Biophys Res Commun. 2020 Jun 11;526(4):1054-1060. doi: 10.1016/j.bbrc.2020.03.184. Epub 2020 Apr 16.
Cyclosporins B, C, D, and E were characterized by NMR spectroscopy, and backbone flexibility was studied by molecular dynamics simulation. Structures of the molecules were characterized by nuclear Overhauser effect spectroscopy, which revealed that the studied peptides have many common features. Molecular dynamics simulation showed that the backbone of cyclosporin E is relatively more rigid than in other peptides. Calcium-dependent swelling of liver mitochondria under the influence of four considered compounds was also investigated. Three of them were found to have the activity similar to cyclosporin A, inhibiting opening of the mitochondrial pore at concentrations within 100-300 nM. However, cyclosporin E did not show any biological effect at concentrations up to 1 μM. Results of this study agree with the idea on the correlation between the peptide chain flexibility and its bioavailability.
环孢菌素 B、C、D 和 E 通过 NMR 光谱学进行了表征，并通过分子动力学模拟研究了其构象柔韧性。通过核磁共振波谱法揭示了这些肽具有许多共同特征，从而确定了分子的结构。分子动力学模拟表明，与其他肽相比，环孢菌素 E 的主链相对更具刚性。还研究了在四种考虑的化合物的影响下，钙离子依赖的肝线粒体肿胀。结果发现，其中三种化合物的活性与环孢菌素 A 相似，在 100-300 nM 的浓度范围内抑制线粒体孔的开放。然而，在高达 1 μM 的浓度下，环孢菌素 E 没有显示出任何生物学效应。该研究结果与肽链柔韧性与其生物利用度之间存在相关性的观点一致。
