Interaction of the pitavastatin with model membranes

Guzel S Shurshalova; Holger A Scheidt; Markus Fischer; Daniel Huster; Albert V Aganov; Vladimir V Klochkov

doi:10.1016/j.bbrep.2021.101143

Interaction of the pitavastatin with model membranes

Biochem Biophys Rep. 2021 Sep 29:28:101143. doi: 10.1016/j.bbrep.2021.101143. eCollection 2021 Dec.

Authors

Guzel S Shurshalova^{1

2}, Holger A Scheidt¹, Markus Fischer¹, Daniel Huster¹, Albert V Aganov², Vladimir V Klochkov²

Affiliations

¹ Institute for Medical Physics and Biophysics, Leipzig University, Härtelstr. 16-18, D-04107 Leipzig, Germany.
² Institute of Physics, Kazan (Volga Region) Federal University, 18 Kremlevskaya St., 420008 Kazan, Russian Federation.

Abstract

Pitavastatin is a statin drug that, by competitively inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase, can lower serum cholesterol levels of low-density lipoprotein (LDL) accompanied by side effects due to pleiotropic effects leading to statin intolerance. These effects can be explained by the lipophilicity of statins, which creates membrane affinity and causes statin localization in cellular membranes. In the current report, the interaction of pitavastatin with POPC model membranes and its influence on the membrane structure were investigated using H, H and P solid-state NMR spectroscopy. Our experiments show the average localization of pitavastatin at the lipid/water interface of the membrane, which is biased towards the hydrocarbon core in comparison to other statin molecules. The membrane binding of pitavastatin also introduced an isotropic component into the ³¹P NMR powder spectra, suggesting that some of the lamellar POPC molecules are converted into highly curved structures.

Keywords: MAS NMR; Model membrane; Order parameters; POPC bilayer; Statin.