Comparison of the cyclosporine variants A and D by NMR spectroscopy

A natural variant of cyclosporine A, cyclosporine D, has been studied using high-resolution NMR spectroscopy in a non-polar solution (chloroform). A complete assignment of the 1H and 13C NMR signals has been made. A comparative analysis of the obtained spectra with the data on cyclosporine A has revealed certain differences between these two peptides, which are most noticeable in the chemical shifts of the atoms of the main chain of residues 5, 8 and the appearance of the hydrogen bond in residue 1. Cyclosporine D is slightly different from CsA in its spectral parameters, but it shows practically no immunological activity. The presented results fill in the gap in the NMR data for cyclosporine variants other than CsA and provide more details about the differences between the peptide variants that may be responsible for their different biological activity

Features of spatial structures of cyclosporins D, E and G revealed by NMR and MD simulations

Cyclosporins D, E and G were characterised by NMR spectroscopy, and backbone flexibility was studied by molecular dynamics simulation. Structures of the molecules were characterised by nuclear Overhauser effect spectroscopy, which revealed that the studied peptides have many common features. Molecular dynamics simulation showed that nanosecond dynamics of the backbone occurs in all cyclosporins, except CsE, which raised a question of how it can influence its biological activity

Comparison of cyclosporin variants B–E based on their structural properties and activity in mitochondrial membranes

© 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