Аннотации:
© 2020 Elsevier Inc. 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.