Keidel S, Szardenings M, Mueller W H
Department of Biochemistry, Medizinische Hochschule Hannover, Federal Republic of Germany.
Eur J Biochem. 1993 Feb 15;212(1):13-26. doi: 10.1111/j.1432-1033.1993.tb17627.x.
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.
合成了几种已知的和一些新的类视黄醇，并通过一种基于诱导P19畸胎瘤细胞、人前列腺癌细胞和新生大鼠心脏细胞原代培养物中碱性磷酸酶的测定方法，研究了它们的体内活性。本研究中使用的测定方法被发现具有可重复性，并且对于快速筛选具有生物活性的类视黄醇很有用。两种新合成的化合物表现出高生物活性。通过Charsorb结合测定法，将这些化合物的生物活性与其结合重组视黄酸受体α和细胞视黄酸结合蛋白I的能力进行了比较。在所研究的三种细胞系中均可检测到两种视黄酸结合蛋白的mRNA。正如从不同视黄酸受体的数量所预期的那样，结果表明类视黄醇不需要结合视黄酸受体α或细胞视黄酸结合蛋白I就能表现出生物活性，但大多数所研究的类视黄醇在与这些蛋白的结合及其生物活性之间显示出明显的相关性。
