Conformational studies of novel estrogen receptor ligands by 1D and 2D NMR spectroscopy and computational methods

Albert B. Sebag, Robert N. Hanson, David A. Forsyth, Choon Young Lee

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

The solution conformations of the novel estrogen receptor ligands (17α,20E)-(p-trifluoromethylphenyl)vinylestradiol (1) and (17α,20E)-(o-trifluoromethylphenyl)vinylestradiol (2) were investigated in 2D and 1D NOESY studies and by comparison of 13C NMR chemical shifts with theoretical shieldings. The 1H and 13C assignments of 1 and 2 were determined by DEPT, COSY and HMQC experiments. The conformations of the 17α-phenylvinyl substituents of 1 and 2 are of interest because of their differing receptor binding affinities and effects in in vivo uterotrophic growth assays. A statistical method of evaluating contributing conformers of 1 and 2 from predicted 13C shifts of possible structures correlated fairly well with conformational conclusions derived from the NOE data. The 17α substituents of 1 and 2 apparently exist in similar conformational equilibria, suggesting that while 1 and 2 would occupy a similar receptor volume, interactions with the protein may shift the equilibrium and thereby influence the expression of the ligand.

Original languageEnglish
Pages (from-to)246-252
Number of pages7
JournalMagnetic Resonance in Chemistry
Volume41
Issue number4
DOIs
StatePublished - Apr 1 2003

Keywords

  • 1D NOESY
  • 2D NOESY
  • COSY
  • Conformational studies
  • DEPT
  • Estrogen receptor ligands
  • HMQC
  • NMR

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