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Conformational studies of novel estrogen receptor ligands by 1D and 2D NMR spectroscopy and computational methods
Author(s) -
Sebag Albert B.,
Hanson Robert N.,
Forsyth David A.,
Lee Choon Young
Publication year - 2003
Publication title -
magnetic resonance in chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.483
H-Index - 72
eISSN - 1097-458X
pISSN - 0749-1581
DOI - 10.1002/mrc.1150
Subject(s) - chemistry , conformational isomerism , two dimensional nuclear magnetic resonance spectroscopy , nuclear magnetic resonance spectroscopy , stereochemistry , estrogen receptor , chemical shift , ligand (biochemistry) , receptor , molecule , biochemistry , organic chemistry , cancer , medicine , breast cancer
The solution conformations of the novel estrogen receptor ligands (17α,20 E )‐( p ‐trifluoromethylphenyl)vinylestradiol ( 1 ) and (17α,20 E )‐( o ‐trifluoromethylphenyl)vinylestradiol ( 2 ) were investigated in 2D and 1D NOESY studies and by comparison of 13 C NMR chemical shifts with theoretical shieldings. The 1 H and 13 C 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 13 C 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. Copyright © 2003 John Wiley & Sons, Ltd.