Distributions of therapeutically promising neurosteroids in cellular membranes
Jazyk angličtina Země Irsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
28043845
DOI
10.1016/j.chemphyslip.2016.12.004
PII: S0009-3084(16)30211-0
Knihovny.cz E-zdroje
- Klíčová slova
- Chromatography, Membranes, Molecular dynamics, N-Methyl-d-aspartate receptors, Steroids,
- MeSH
- buněčná membrána chemie MeSH
- kvantová teorie MeSH
- molekulární konformace MeSH
- neurotransmiterové látky chemie MeSH
- permeabilita MeSH
- simulace molekulární dynamiky MeSH
- termodynamika MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- neurotransmiterové látky MeSH
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.
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