title: 17β-estradiol (E2) in membranes: Orientation and dynamic properties.
abstract: Non-genomic membrane effects of estrogens are of great interest because of the diverse biological activities they may elicit. To further our understanding of the molecular features of the interaction between estrogenic hormones and membrane bilayers, we have determined the preferred orientation, location, and dynamic properties of 17β-estradiol (E2) in two different phospholipid membrane environments using (2)H-NMR and 2D (1)H-(13)C HSQC in conjunction with molecular dynamics simulations. Unequivocal spectral assignments to specific (2)H labels were made possible by synthesizing six selectively deuterated E2 molecules. The data allow us to conclude that the E2 molecule adopts a nearly "horizontal" orientation in the membrane bilayer with its long axis essentially perpendicular to the lipid acyl-chains. All four rings of the E2 molecule are located near the membrane interface, allowing both the E2 3-OH and the 17β-OH groups to engage in hydrogen bonding and electrostatic interactions with polar phospholipid groups. The findings augment our knowledge of the molecular interactions between E2 and membrane bilayer and highlight the asymmetric nature of the dynamic motions of the rigid E2 molecule in a membrane environment.
authors.affiliation: Center for Drug Discovery, Department of Pharmaceutical Sciences, Northeastern University, 360 Huntington Avenue, Boston, MA 02115-5000, USA; Department of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Avenue, Boston, MA 02115-5000, USA. Electronic address: j.guo@neu.edu.
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Guo
authors.affiliation: Physics Department, College of the Holy Cross, 1 College Street, Worcester, MA 01610, USA.
authors.forename: De-Ping
authors.initials: DP
authors.lastname: Yang
authors.affiliation: Center for Drug Discovery, Department of Pharmaceutical Sciences, Northeastern University, 360 Huntington Avenue, Boston, MA 02115-5000, USA; Department of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Avenue, Boston, MA 02115-5000, USA.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Tian
authors.affiliation: Center for Drug Discovery, Department of Pharmaceutical Sciences, Northeastern University, 360 Huntington Avenue, Boston, MA 02115-5000, USA; Department of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Avenue, Boston, MA 02115-5000, USA.
authors.forename: V Kiran
authors.initials: VK
authors.lastname: Vemuri
authors.affiliation: Center for Drug Discovery, Department of Pharmaceutical Sciences, Northeastern University, 360 Huntington Avenue, Boston, MA 02115-5000, USA; Department of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Avenue, Boston, MA 02115-5000, USA.
authors.forename: Dali
authors.initials: D
authors.lastname: Yin
authors.affiliation: Center for Drug Discovery, Department of Pharmaceutical Sciences, Northeastern University, 360 Huntington Avenue, Boston, MA 02115-5000, USA; Department of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Avenue, Boston, MA 02115-5000, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Li
authors.affiliation: Center for Drug Discovery, Department of Pharmaceutical Sciences, Northeastern University, 360 Huntington Avenue, Boston, MA 02115-5000, USA; Department of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Avenue, Boston, MA 02115-5000, USA.
authors.forename: Richard I
authors.initials: RI
authors.lastname: Duclos
authors.affiliation: Center for Drug Discovery, Department of Pharmaceutical Sciences, Northeastern University, 360 Huntington Avenue, Boston, MA 02115-5000, USA; Department of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Avenue, Boston, MA 02115-5000, USA.
authors.forename: Lingling
authors.initials: L
authors.lastname: Shen
authors.affiliation: Center for Drug Discovery, Department of Pharmaceutical Sciences, Northeastern University, 360 Huntington Avenue, Boston, MA 02115-5000, USA; Department of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Avenue, Boston, MA 02115-5000, USA.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Ma
authors.affiliation: Center for Drug Discovery, Department of Pharmaceutical Sciences, Northeastern University, 360 Huntington Avenue, Boston, MA 02115-5000, USA; Department of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Avenue, Boston, MA 02115-5000, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Janero
authors.affiliation: Center for Drug Discovery, Department of Pharmaceutical Sciences, Northeastern University, 360 Huntington Avenue, Boston, MA 02115-5000, USA; Department of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Avenue, Boston, MA 02115-5000, USA. Electronic address: a.makriyannis@neu.edu.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Makriyannis
mesh_terms: D004958:Estradiol / Q000737:chemistry*; D008567:Membranes, Artificial; D056004:Molecular Dynamics Simulation
chemical_list: D008567:Membranes, Artificial; D004958:Estradiol
keywords: Biomembranes; Drugs; Estrogen; NMR; Phospholipids; Relaxation agents