In vivo biological activity of retinoids partially correlates to their affinity to recombinant retinoic-acid receptor alpha and recombinant-cellular retinoic-acid-binding protein I.
Several known and some new retinoids were synthesized and their in vivo activity was investigated by an assay, based on induction of alkaline phosphatase in P19 teratocarcinoma cells, human prostate carcinoma cells and primary cultures of neonatal rat heart cells. The assay used in this study was found to be reproducible and useful for rapid screening of retinoids for biological activity. Two newly synthesized compounds exhibit high biological activity. The biological potency of the compounds was compared to their ability to bind to recombinant retinoic-acid receptor alpha and to cellular retinoic-acid-binding protein I determined by Charsorb-binding assay. mRNA of both retinoic-acid-binding proteins could be detected in the three cell lines investigated. As expected from the number of different retinoic-acid receptors, the results suggest that retinoids do not need to bind retinoic-acid receptor alpha nor cellular retinoic-acid-binding protein I in order to exhibit biological activity, but most retinoids investigated show a clear correlation between binding to these proteins and their biological activity.
Department of Biochemistry, Medizinische Hochschule Hannover, Federal Republic of Germany.
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S
Keidel
M
M
Szardenings
W H
WH
Mueller
D000469:Alkaline Phosphatase / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D001681:Biological Assay; D002352:Carrier Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D018168:Receptors, Retinoic Acid; D011994:Recombinant Proteins / Q000378:metabolism; D012176:Retinoids / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D011994:Recombinant Proteins; D012176:Retinoids; D000469:Alkaline Phosphatase