Abstract
The synthetic estrogen diethylstilbestrol (DES) is used to treat metastatic carcinomas and prostate cancer. We studied its interaction with membranes and its localization to understand its mechanism of action and side-effects. We used differential scanning calorimetry (DSC) showing that DES fluidized the membrane and has poor solubility in DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) in the fluid state. Using small-angle X-ray diffraction (SAXD), it was observed that DES increased the thickness of the water layer between phospholipid membranes, indicating effects on the membrane surface. DSC, X-ray diffraction, and 31P-NMR spectroscopy were used to study the effect of DES on the Lα-to-HII phase transition, and it was observed that negative curvature of the membrane is promoted by DES, and this effect may be significant to understand its action on membrane enzymes. Using the 1H-NOESY-NMR-MAS technique, cross-relaxation rates for different protons of DES with POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) protons were calculated, suggesting that the most likely location of DES in the membrane is with the main axis parallel to the surface and close to the first carbons of the fatty acyl chains of POPC. Molecular dynamics simulations were in close agreements with the experimental results regarding the location of DES in phospholipids bilayers.
Highlights
IntroductionDiethylstilbestrol (DES)(DES) is is aa synthetic synthetic form form of of estrogen, estrogen, aa female female hormone. hormone
A POPC membrane was used here as a membrane matrix for the location of DES molecule in the membrane by using 2D-NOESY 1H-MAS-NMR; the advantage of using this phospholipid is that it possesses a double bond in the oleoyl chain, to facilitate the formation of nonlamellar structures and to induce negative curvature in the membrane [31,41,42]
A POPC membrane was used here as a membrane matrix for the location of DES molecule in the membrane by using 2D-NOESY 1 H-MAS-NMR; the advantage of using this phospholipid is that it possesses a double bond in the oleoyl chain, and this offers a reference point in the middle of the monolayer, whereas saturated fatty acyl chains do not have this advantage, whereby only protons bound to carbons 2 and 3 and to the last carbon can be differentiated
Summary
IntroductionDiethylstilbestrol (DES)(DES) is is aa synthetic synthetic form form of of estrogen, estrogen, aa female female hormone. hormone.
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