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Vitamin D: Structure‐function analyses and the design of analogs
Author(s) -
Okamura William H.,
Palenzuela J. Antonio,
Plumet Joaquin,
Midland M. Mark
Publication year - 1992
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240490104
Subject(s) - side chain , function (biology) , computational biology , chemistry , chain (unit) , stereochemistry , computer science , biology , physics , microbiology and biotechnology , organic chemistry , astronomy , polymer
There is continuing and emerging new interest in the development of vitamin D analogs resulting from the recognition that analogs of 1α,25‐dihydroxyvitamin D 3 [1α,25‐(OH) 2 D 3 ] may be therapeutically useful. Side chain analogs of this steroid hormone are of particular interest because a family of lead structures have recently emerged for possible use in the treatment of certain types of cancers and skin diseases. Because of the chaotic array of side chain structures which exhibit useful therapeutic indices for these purposes, a more systematic approach towards developing intelligible structure‐function information needs development. Accordingly, a method has been devised to analyze analogs as to their side chain topology based on identifying specific occupancy volumes through conformational analysis. Dot maps have been constructed as an indication of the volume in space which the side chain of 1α,25‐(OH) 2 ‐D 3 or analogs is permitted to occupy. Volume exclusion analyses based on comparison of structural and biological data for 1α,257‐(OH) 2 ‐D 3 and analogs are anticipated to lead to a more cogent model for drug design. A cautionary note on the limitations of this approach is discussed.