Distributions of therapeutically promising neurosteroids in cellular membranes

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/61388963:_____/17:00475164 RIV/60461373:22310/17:43902828

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Distributions of therapeutically promising neurosteroids in cellular membranes

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Distributions of therapeutically promising neurosteroids in cellular membranes

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Chemistry and Physics of Lipids

ISSN

0009-3084

e-ISSN

—

Svazek periodika

203

Číslo periodika v rámci svazku

Mar

Stát vydavatele periodika

IE - Irsko

Počet stran výsledku

9

Strana od-do

78-86

Kód UT WoS článku

000395725500009

EID výsledku v databázi Scopus

2-s2.0-85010992297