Journal article
Steroid structure and function—IX. Molecular conformation and receptor binding of isomeric analogs of d-Homo-Estradiol
Journal of steroid biochemistry, Vol.14(1), pp.1-7
1981
DOI: 10.1016/0022-4731(81)90185-0
PMID: 7206693
Abstract
The fact that
rac-
d-homo-8α-estra-1,3,5(10)-triene-3,17a-diol (DH8α) has a higher affinity for the estrogen receptor in rabbit uterus than
rac-
d-homo-estra-1,3,5(10)-triene-3,17a-diol (DH8β) may be due to differences in hydrogen bonding potential of the C(3) hydroxyl due to conformational transmission effects. The crystal structure determinations of DH8α and DH8β reported here unambiguously establish the relative configurations of the two structures and show that the difference in the binding affinity is not due to a change in O(3)–O(17) distance. The greater affinity of DH8α, estradiol, and diethylstilbestrol (DES) may be linked to an enhanced potential to act as hydrogen bond acceptors as well as donors in the active site. Crystallographic evidence suggests that the weaker binding DH8β and estrone act as donors only. Quantum calculations suggest that the energy of a sequential pair of hydrogen bonds is not merely additive (≅6 Kcal/mol) but may be as much as 9 Kcal/mol. These results support the hypothesis that there is a highly specific association between the A-rings and the binding site of the estrogen receptor protein involving O(3) as a hydrogen bond donor and acceptor and that the receptor accommodates greater variability in the
d-ring region.
Details
- Title: Subtitle
- Steroid structure and function—IX. Molecular conformation and receptor binding of isomeric analogs of d-Homo-Estradiol
- Creators
- William L. Duax - The Medical FoundationG.David Smith - Institute of Bioorganic ChemistryDale C. Swenson - The Medical FoundationPhyllis D. Strong - The Medical FoundationCharles M. Weeks - Institute of Bioorganic ChemistryS.N. Ananchenko - Institute of Bioorganic ChemistryV.V. Egorova - Medical Foundation of Buffalo, Inc. 73 High Street, Buffalo, New York 14203, U.S.A
- Resource Type
- Journal article
- Publication Details
- Journal of steroid biochemistry, Vol.14(1), pp.1-7
- Publisher
- Elsevier B.V
- DOI
- 10.1016/0022-4731(81)90185-0
- PMID
- 7206693
- ISSN
- 0022-4731
- Language
- English
- Date published
- 1981
- Academic Unit
- Chemistry
- Record Identifier
- 9984622749302771
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