Distributions of therapeutically promising neurosteroids in cellular membranes

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388955%3A_____%2F17%3A00475164" target="_blank" >RIV/61388955:_____/17:00475164 - isvavai.cz</a>
Alternative codes found
RIV/61388963:_____/17:00475164 RIV/60461373:22310/17:43902828
Result on the web
<a href="http://dx.doi.org/10.1016/j.chemphyslip.2016.12.004" target="_blank" >http://dx.doi.org/10.1016/j.chemphyslip.2016.12.004</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.chemphyslip.2016.12.004" target="_blank" >10.1016/j.chemphyslip.2016.12.004</a>

Result language
angličtina
Original language name
Distributions of therapeutically promising neurosteroids in cellular membranes
Original language description
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 steroids, 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 steroids toward membrane-bound N-Methyl-D-aspartate receptors.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10403 - Physical chemistry

Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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