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Fig. 4. Overlaid structures of the analog 2 in the preferred conformation (black)
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complex with VDR. A minimum energy conformation of the ana-
log 2 closely resembles that found in the crystalline complex of
the natural hormone and VDR (Fig. 4). The distances between the
respective oxygen atoms in both structures are smaller than 1 Å.
The results of testing the ability of the synthesized analog 2 to
bind vitamin D receptor fully confirmed our expectations. A pres-
ence of bulky 6-methyl substituent did not diminish the affinity of
compound to the receptor. Because the synthesized analog binds
VDR very effectively but has a markedly lower potency in biologi-
cal activities downstream from receptor binding, it is possible that
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Acknowledgements
The work was supported in part by funds from the Wisconsin
Alumni Research Foundation. Special thanks are addressed to Jean
Prahl and Jennifer Vaughan for carrying out the in vitro studies.
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