Steroid binding to the cytosolic estrogen receptor from rat uterus. influence of the orientation of substituents in the 17-position of the 8β- and 8α-series

Kaspar, Peter; Witzel, Herbert

doi:10.1016/0022-4731(85)90403-0

Cited by 23 publications

(5 citation statements)

References 21 publications

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“…From SAR data for different organisms it is well-established that the two hydroxyl groups of E2 contribute differently to the binding affinity . The removal of 17β-OH reduces the binding affinity toward rERα by a factor of 44 (relative binding affinity, RBA = 1.9%). An even weaker binding is observed in the absence of 3-OH.…”

Section: Resultsmentioning

confidence: 99%

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Three-Dimensional Models of Estrogen Receptor Ligand Binding Domain Complexes, Based on Related Crystal Structures and Mutational and Structure−Activity Relationship Data

et al. 1998

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On the basis of the recently determined crystal structures of the ligand binding domains (LBDs) of the retinoic acid nuclear receptors (NRs), we present a three-dimensional (3D) molecular model of the human estrogen receptor alpha (hERalpha) LBD. A literature search for mutants affecting the binding properties has been performed; 45 out of 48 published mutants can be explained satisfactorily on the basis of the model. Estradiol has been docked into the binding pocket to probe its interactions with the protein. Energy minimizations and molecular dynamics calculations were performed for various ligand orientations. To evaluate their quality, the different models were scored using known structure-activity relationship (SAR) data for selected close estradiol homologues. The two best models explain largely the binding affinities of more distantly related ligands.

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Section: Resultsmentioning

confidence: 99%

“…However, the observed binding behavior of the double mutant is in agreement with the expected effect of the D351V mutation. binding affinity toward rERR by a factor of 44 (relative binding affinity, RBA ) 1.9% 35 ). An even weaker binding is observed in the absence of 3-OH.…”

Section: Resultsmentioning

confidence: 99%

Three-Dimensional Models of Estrogen Receptor Ligand Binding Domain Complexes, Based on Related Crystal Structures and Mutational and Structure−Activity Relationship Data

et al. 1998

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“…For this reason, we used tamoxifen, a estrogen receptor blocker to determine if the effects of estradiol-ethylenediamine derivative on perfusion pressure were via the estrogen receptor. Interaction of estradiol-ethylenediamine derivative with the estrogen-receptor, may be a key requirement for the biological activity as in the case of other estradiol derivatives 31,32 . Our results showed that the effects of estradiol-ethylenediamine derivative were not inhibited by tamoxifen, suggesting that the molecular mechanism is not via the estrogen-receptor.…”

Section: Discussionmentioning

confidence: 99%

Changes Induced by Estradiol-Ethylenediamine Derivative on Perfusion Pressure and Coronary Resistance in Isolated Rat Heart: L-Type Calcium Channel

Figueroa‐Valverde¹,

Cedillo²,

Ramos³

et al. 2011

BIOMED PAP

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Aim. The present study was designed to investigate the effects of estradiol-ethylenediamine derivative on perfusion pressure and coronary resistance in rats. An additional aim was to identify the molecular mechanisms involved.Methods. The Langendorff model was used to measure perfusion pressure and coronary resistance changes in isolated rat heart after estradiol-ethylenediamine derivative alone and following compounds; tamoxifen (estrogen receptor antagonist), prazosin (alpha1 adrenoreceptor antagonist), metoprolol (selective beta1 receptor blocker), indomethacin (prostanglandin synthesis inhibitor) and nifedipine (L-type calcium-channel inhibitor).Results. The results show that estradiol-ethylenediamine derivative [10 -9 mmol] significantly increased perfusion pressure (p = 0.005) and coronary resistance (p = 0.006) in isolated rat heart. Additionally, the effect of estradiolethylenediamine on perfusion pressure [10 -9 to 10 -4 mmol] was only blocked in the presence of the L-type calciumchannel (nifedipine).Conclusions. These data suggest that the effect of estradiol-ethylenediamine on perfusion pressure and vascular coronary involves activation of the L-type calcium channel through a non-genomic molecular mechanism.

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“…The mass-spectral fragmentation of the CEDMS derivative of cholesterol has been illustrated. Mass spectrometry has been used to characterize 16-amino-oestrogen derivative^'^^ and metabolites of the aromatase inhibitor 4-hydroxyandrost-4ene-3,17-dione.lg1 Fragment ions (24), formed via a retro-Diels-Alder reaction, were observed in the mass spectra of a series of oestra-1,3,5( 10)-trienes. lS2 Protium-deuterium exchanges were observed in the E.I.…”

Section: Mass Spectrometry and Gas Chromatogra Phy-mass Spectrometrymentioning

confidence: 99%

Steroids: physical methods

Kirk¹

1989

Nat. Prod. Rep.

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Steroid binding to the cytosolic estrogen receptor from rat uterus. influence of the orientation of substituents in the 17-position of the 8β- and 8α-series

Cited by 23 publications

References 21 publications

Three-Dimensional Models of Estrogen Receptor Ligand Binding Domain Complexes, Based on Related Crystal Structures and Mutational and Structure−Activity Relationship Data

Three-Dimensional Models of Estrogen Receptor Ligand Binding Domain Complexes, Based on Related Crystal Structures and Mutational and Structure−Activity Relationship Data

Changes Induced by Estradiol-Ethylenediamine Derivative on Perfusion Pressure and Coronary Resistance in Isolated Rat Heart: L-Type Calcium Channel

Steroids: physical methods

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