Synthesis and androgen receptor binding of dihydrotestosterone hemisuccinate homologs.
Dihydrotestosterone-succinyl-agarose is the most common form of androgen affinity column. To investigate the effect of variation in the number of methylene groups between the ester and amide functions, a homologous series, varying the number of methylenes between the functional groups, has been synthesized and evaluated. In addition, since structure studies show 17 alpha-methyldihydrotestosterone binds with high affinity, a 17 alpha-carboxymethyl ligand (3) was studied. Relative binding affinities of the dicarboxylates (assayed as the n-butyl amides) range from 0.003 to 0.044 (dihydrotestosterone = 1.00), while there was no detectable binding for 3. Only the suberate binds better than the much-used succinate, and it would be a likely candidate for an affinity ligand.
Stobaugh
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ME
Department of Biochemistry, Indiana University School of Medicine, Veterans Administration Medical Center, Indianapolis 46202.
Blickenstaff
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RT
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D002846:Chromatography, Affinity; D013196:Dihydrotestosterone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D008297:Male; D008745:Methylation; D015394:Molecular Structure; D051381:Rats; D011919:Rats, Inbred Strains; D011944:Receptors, Androgen / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013386:Succinates / Q000138:chemical synthesis* / Q000378:metabolism
D011944:Receptors, Androgen; D013386:Succinates; D013196:Dihydrotestosterone; C008376:mestanolone