25-30 August 2019
Henry Ford Building
Europe/Berlin timezone

Different variants of cyclosporin studied by NMR: Molecular structure and conformational flexibility

Not scheduled
4h
Harnack House and Henry Ford Building

Harnack House and Henry Ford Building

Board: 105
Poster Posters

Speaker

Dr Sergey Efimov (Kazan Federal University)

Description

Cyclosporin A, well known as an immunosuppressive agent, is one of a family of congeners synthesised in certain soil fungi. Three natural variants of cyclosporin (B, C, D) were studied by high resolution NMR spectroscopy in chloroform and dimethyl formamide. CsB has alanine in position 2 instead of $\alpha$-aminobutyric acid (Abu2) found in CsA, in CsC this residue is replaced by threonine, and in CsD, by valine.
In general, obtained spectra of the peptides are alike. However, there are some differences seen in $^{1}$H and 2D $^{1}$H,$^{13}$C-HSQC spectra. For instance, the OH proton of residue Thr2 in CsC is visible in CDCl$_{3}$ at 298 K, as well as the OH proton of Bmt1 in CsD. In CsA and CsB, however, hydroxyl protons were not observed directly due to the exchange. CsD was also found to have negligible signals of the minor conformer, while it is clearly seen in the spectra of other three compounds.
Structural data were obtained from ROESY spectra, which allowed building model structures of the investigated molecules.
The case of chemical exchange was considered on the example of CsC in DMF. The pattern of exchange resembles that observed for CsA in polar media such as DMSO. Signals of the NH protons were assigned, and temperature behaviour of their chemical shifts was analysed. It was found that most of the observed conformers have lost their intramolecular H-bonds. Cis-trans isomerisation of the peptide bonds was suggested to be the reason of the conformational exchange.
The work was funded by the Russian Science Foundation (project no. 18-73-10088).

Survase S.A., Kagliwal L.D., Annapure U.S., Singhal R.S.: Biotechnol. Adv. 2011, 29, 418-435.
Efimov S.V., Zgadzay Yu.O., Darwish S., Klochkov V.V.: BioNanoScience. 2019, 10.1007/s12668-019-00641-z

Primary authors

Dr Sergey Efimov (Kazan Federal University) Mr Yuriy Zgadzay (Kazan Federal University) Dr Ilya Khodov (Kazan Federal University) Prof. Vladimir Klochkov (Kazan Federal University)

Presentation Materials