Tampere University of Technology

TUTCRIS Research Portal

Distributions of Therapeutically Promising Steroids in Cellular Membranes

Research output: Contribution to journalArticleScientificpeer-review


Original languageEnglish
Pages (from-to)78-86
Number of pages8
JournalChemistry and Physics of Lipids
Early online date30 Dec 2016
Publication statusPublished - Mar 2017
Publication typeA1 Journal article-refereed


Abstract Interactions of two neurosteroids, inhibiting membrane-bound N-Methyl-d-aspartate receptors, with phospholipid membranes are studied. Namely, endogenous pregnanolone sulfate is compared with pregnanolone glutamate, the latter being a novel synthetic steroidal inhibitor of these receptors with potential pharmaceutical use. Molecular-level details of steroid-phospholipid membranes interactions are scrutinized employing molecular dynamics simulations supported by quantum chemical calculations to assess steroid lipophilicity. Moreover, permeability of both species across membranes is experimentally evaluated by immobilized artificial membrane chromatography. We demonstrate that while there is no significant difference of lipophilicity and membrane permeability between the two sterols, they differ significantly regarding detailed localization in phospholipid membranes. The bulky glutamate moiety of pregnanolone glutamate is flexible and well exposed to the water phase while the sulfate group of pregnanolone sulfate is hidden in the membrane headgroup region. This dissimilarity of behavior in membranes can potentially account for the observed different activities of the two sterols toward membrane-bound N-Methyl-d-aspartate receptors.


  • steroids, N-Methyl-d-aspartate receptors, membranes, molecular dynamics, chromatography

Publication forum classification

Field of science, Statistics Finland