FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2607356885> ?p ?o ?g. }

• W2607356885 endingPage "347" @default.
• W2607356885 startingPage "334" @default.
• W2607356885 abstract "Neuroactive steroids are potent positive allosteric modulators of GABAA receptors (GABAAR), but the locations of their GABAAR binding sites remain poorly defined. To discover these sites, we synthesized two photoreactive analogs of alphaxalone, an anesthetic neurosteroid targeting GABAAR, 11β-(4-azido-2,3,5,6-tetrafluorobenzoyloxy)allopregnanolone, (F4N3Bzoxy-AP) and 11-aziallopregnanolone (11-AziAP). Both photoprobes acted with equal or higher potency than alphaxalone as general anesthetics and potentiators of GABAAR responses, left-shifting the GABA concentration – response curve for human α1β3γ2 GABAARs expressed in Xenopus oocytes, and enhancing [3H]muscimol binding to α1β3γ2 GABAARs expressed in HEK293 cells. With EC50 of 110 nM, 11-AziAP is one the most potent general anesthetics reported. [3H]F4N3Bzoxy-AP and [3H]11-AziAP, at anesthetic concentrations, photoincorporated into α- and β-subunits of purified α1β3γ2 GABAARs, but labeling at the subunit level was not inhibited by alphaxalone (30 μM). The enhancement of photolabeling by 3H-azietomidate and 3H-mTFD-MPAB in the presence of either of the two steroid photoprobes indicates the neurosteroid binding site is different from, but allosterically related to, the etomidate and barbiturate sites. Our observations are consistent with two hypotheses. First, F4N3Bzoxy-AP and 11-aziAP bind to a high affinity site in such a pose that the 11-photoactivatable moiety, that is rigidly attached to the steroid backbone, points away from the protein. Second, F4N3Bzoxy-AP, 11-aziAP and other steroid anesthetics, which are present at very high concentration at the lipid-protein interface due to their high lipophilicity, act via low affinity sites, as proposed by Akk et al. (Psychoneuroendocrinology 2009, 34S1, S59-S66)." @default.
• W2607356885 created "2017-04-28" @default.
• W2607356885 creator A5009063782 @default.
• W2607356885 creator A5011083469 @default.
• W2607356885 creator A5014863753 @default.
• W2607356885 creator A5019912497 @default.
• W2607356885 creator A5027809084 @default.
• W2607356885 creator A5031155872 @default.
• W2607356885 creator A5033630229 @default.
• W2607356885 creator A5050184660 @default.
• W2607356885 creator A5065081270 @default.
• W2607356885 creator A5066540747 @default.
• W2607356885 creator A5075377045 @default.
• W2607356885 creator A5078870163 @default.
• W2607356885 date "2017-08-01" @default.
• W2607356885 modified "2023-10-18" @default.
• W2607356885 title "Synthesis and pharmacological evaluation of neurosteroid photoaffinity ligands" @default.
• W2607356885 cites W1668870376 @default.
• W2607356885 cites W1865188258 @default.
• W2607356885 cites W1972584910 @default.
• W2607356885 cites W1976213326 @default.
• W2607356885 cites W1976924361 @default.
• W2607356885 cites W1979539714 @default.
• W2607356885 cites W1983756509 @default.
• W2607356885 cites W1986166766 @default.
• W2607356885 cites W1998765262 @default.
• W2607356885 cites W2017227716 @default.
• W2607356885 cites W2028203662 @default.
• W2607356885 cites W2046777332 @default.
• W2607356885 cites W2052286050 @default.
• W2607356885 cites W2056061463 @default.
• W2607356885 cites W2057387160 @default.
• W2607356885 cites W2062076510 @default.
• W2607356885 cites W2063157730 @default.
• W2607356885 cites W2070510853 @default.
• W2607356885 cites W2074287295 @default.
• W2607356885 cites W2074957858 @default.
• W2607356885 cites W2075202060 @default.
• W2607356885 cites W2076224060 @default.
• W2607356885 cites W2079618712 @default.
• W2607356885 cites W2080245295 @default.
• W2607356885 cites W2085396840 @default.
• W2607356885 cites W2086498140 @default.
• W2607356885 cites W2087030807 @default.
• W2607356885 cites W2089409459 @default.
• W2607356885 cites W2091486815 @default.
• W2607356885 cites W2092604263 @default.
• W2607356885 cites W2094541230 @default.
• W2607356885 cites W2110462270 @default.
• W2607356885 cites W2124419019 @default.
• W2607356885 cites W2127911860 @default.
• W2607356885 cites W2131961672 @default.
• W2607356885 cites W2140155039 @default.
• W2607356885 cites W2155510699 @default.
• W2607356885 cites W2157231352 @default.
• W2607356885 cites W2170087378 @default.
• W2607356885 cites W2407452661 @default.
• W2607356885 cites W2498390373 @default.
• W2607356885 cites W3191740793 @default.
• W2607356885 doi "https://doi.org/10.1016/j.ejmech.2017.04.043" @default.
• W2607356885 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6071317" @default.
• W2607356885 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28505538" @default.
• W2607356885 hasPublicationYear "2017" @default.
• W2607356885 type Work @default.
• W2607356885 sameAs 2607356885 @default.
• W2607356885 citedByCount "12" @default.
• W2607356885 countsByYear W26073568852018 @default.
• W2607356885 countsByYear W26073568852019 @default.
• W2607356885 countsByYear W26073568852020 @default.
• W2607356885 countsByYear W26073568852021 @default.
• W2607356885 countsByYear W26073568852023 @default.
• W2607356885 crossrefType "journal-article" @default.
• W2607356885 hasAuthorship W2607356885A5009063782 @default.
• W2607356885 hasAuthorship W2607356885A5011083469 @default.
• W2607356885 hasAuthorship W2607356885A5014863753 @default.
• W2607356885 hasAuthorship W2607356885A5019912497 @default.
• W2607356885 hasAuthorship W2607356885A5027809084 @default.
• W2607356885 hasAuthorship W2607356885A5031155872 @default.
• W2607356885 hasAuthorship W2607356885A5033630229 @default.
• W2607356885 hasAuthorship W2607356885A5050184660 @default.
• W2607356885 hasAuthorship W2607356885A5065081270 @default.
• W2607356885 hasAuthorship W2607356885A5066540747 @default.
• W2607356885 hasAuthorship W2607356885A5075377045 @default.
• W2607356885 hasAuthorship W2607356885A5078870163 @default.
• W2607356885 hasBestOaLocation W26073568851 @default.
• W2607356885 hasConcept C107824862 @default.
• W2607356885 hasConcept C118552586 @default.
• W2607356885 hasConcept C15744967 @default.
• W2607356885 hasConcept C166342909 @default.
• W2607356885 hasConcept C168258287 @default.
• W2607356885 hasConcept C170493617 @default.
• W2607356885 hasConcept C185592680 @default.
• W2607356885 hasConcept C2776801781 @default.
• W2607356885 hasConcept C2778162923 @default.
• W2607356885 hasConcept C2778338918 @default.
• W2607356885 hasConcept C2778581200 @default.
• W2607356885 hasConcept C2779188335 @default.
• W2607356885 hasConcept C2780902042 @default.

• next