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Biological effects of retinoic acid (RA) are mediated through its binding to three closely related nuclear receptors (RAR alpha, RAR beta, and RAR gamma) belonging to the steroid-thyroid nuclear receptor family. RARs are able to modulate the transcription of specific genes by binding to responsive elements located in the promoter-enhancer region of these genes. As demonstrated by in situ hybridization, the distribution of each RAR type in the developing embryo, as well as in the adult, is not uniform. In this context, synthetic retinoids that would behave as selective ligands would be invaluable for studying the respective roles of each RAR type in cultured cells, whole animals, and embryos. Moreover, from a pharmacological point of view, such selective compounds may possess a higher therapeutic index and a lower teratogenic risk, because they might affect specific tissues and spare some others. As an approach to this problem, we have set up two complementary assays, (i) an in vitro binding assay to determine the Kd values of retinoids for RAR alpha, RAR beta, and RAR gamma and (ii) a functional assay in cultured cells to evaluate the potential of retinoids to transactivate, through their binding to one type of RAR, a reporter gene. The binding assay uses nuclear extracts of COS-7 cells transfected with vectors expressing RAR alpha, RAR beta, or RAR gamma. The functional assay is a measure of chloramphenicol acetyltransferase (CAT) activity in HeLa cells co-transfected with the expression vectors used in the binding assay and the reporter gene TRE-tk-CAT. Selective agonists for RAR alpha (Am80 and Am580) and RAR beta-RAR gamma (CD495 and CD564) were identified. However, compounds with pure RAR beta or RAR gamma selectivity have not yet been identified.

Triploid and tetraploid Saccharomyces strains containing different combinations of a gua-1 mutant allele and the corresponding wild type were prepared. The cultivation of the different strains in media upon which the mutant fails to grow leads to a pronounced growth rate response to the dosage of the wild-type allele. Proportionality between the specific activity of the guanosine 5'-monophosphate synthetase and the wild-type dosage was reavealed. Inosine 5'-monophosphate dehydrogenase, the precursor enzyme in the pathway, is derepressed in a sigmoid manner when the wild-type dosage is reduced, whereas the activity of cytosine deaminase, investigated as a reference enzyme, is less affected.

Es wird das Mikrowellenspektrum von Fluorwasserstoffassoziaten im X-und K-Band bei -70 °C und 0,01 Torr gemessen und analysiert. Dazu wird ein erstelltes Frequenzprogramm für den asymmetrischen Kreisel verwendet, sowie ein Extrapolationsprogramm, das eine in der Literatur angegebene druck-und temperaturabhängige Verteilung der Fluorwasserstoffassoziate auf für Mikrowellenspektroskopie geeignete Drücke und Temperaturen umzurechnen erlaubt. Es zeigt sich, daß planare hexamere und heptamere Fluorwasserstoffassoziate vorliegen mit F-F-F-Winkeln von etwa 104° und H-F-Bindungslängen von 0,9997 Å bzw. 0,9640 Å. Die Längen der Wasserstoff brücken sind 1,4998 Å bzw. 1,6105 Å. Ein Vergleich der Bindungslängen zeigt, daß bei Anlagerung von H-F an (HF)6eine Kontraktion der Fluorwasserstoffbindung um 3,5% und eine Dilatation der Wasserstoffbrückenbindung um 1% stattfindet. Dieses Ergebnis steht im Einklang mit der oben erwähnten Assoziatverteilung, die eine Minderung der Kettenstabilität beim Übergang von hexamerer zu heptamerer Kette erwarten läßt.