Synthesis of 6-Sulfur Analogues of Oxanosine and Closely Related Derivatives Thereof

Abstract

Novel β-D-ribofuranosides having a 5-substituted imidazo [4,5-d] [1,3]thiazine ring, including the S⁶-congener 3 of oxanosine 2, were synthesized for screening their anticancer and antiviral activities.     

Thermal salivation in rats, anesthetized with barbiturates, chloralose, urethane and ketamine

1. The relationship between thermal salivation (TS) and thermoregulation was studied in anesthetized rats. 2. Of the 6 anesthetics used, ketamine-anesthetized rats secreted the largest amount of saliva. Salivation, however, was thermal and not induced by ketamine itself. 3. Ketamine-anesthetized rats readily secreted saliva at core temperatures less than 40 degrees C but TS was remarkably enhanced by hyperthermia of 40-42.5 degrees C. 4. The equilibrium phase in the triphasic heat response of core temperature was a consequence of equilibrium between heat gain and heat loss by salivation.     

Mechanism of tumor promotion

Various kinds of calmodulin-interacting agents have been proved to suppress tumor promotion in vivo. In this study, we further demonstrate that flunarizine and dehydroepiandrosterone, which are proved to interact with calmodulin, showed antitumor-promoting activity in two-stage carcinogenesis of mouse skin. These results indicate that Ca2+/-calmodulin system, may play an important role in tumor promotion.     

Differences in environment of FAD between NAD-dependent and O2-dependent types of rat liver xanthine dehydrogenase shown by active site probe study

Rat liver deflavoxanthine dehydrogenase has been prepared by incubating native enzyme with calcium chloride. On reconstitution with FAD, about 85% of the original activity is recovered, all which is the O2-dependent type. In contrast, when dithiothreitol-treated deflavoenzyme is incubated with FAD, the recovery of activity is almost the same as above, but most of the recovered activity is of the NAD-dependent type. Deflavoenzyme with or without previous treatment with dithiothreitol was also reconstituted with two artificial FAD analogues, 8-mercapto-FAD and 6-OH-FAD. The difference spectra between the reconstituted enzymes and the initial deflavoenzyme indicate that, in each case, the FAD analogue is bound in its neutral form in dithiothreitol-treated enzyme, whereas it is bound in the anionic form in enzyme without previous dithiothreitol treatment. Furthermore, the protonated forms can be converted into the anionic forms on storage with a concomitant change of activity from the NAD-dependent to the O2-dependent type. This clearly indicates different environments around FAD in the two types of enzyme protein, which are shown to be interconvertible through oxidation-reduction of enzyme cysteinyl residues.     

Synthesis of Guanosine-3′-diphosphate- 5′-diphosphate by Nucleotide Pyrophosphotransferase

An α-glucosidase was purified from sweet corn seeds by fractionation with ammonium sulfate, chromatographies on CM-Sepharose and Sepharose 4B, and gel filtrations on Sephadex G-100. The enzyme was homogeneous in disc electrophoretic analysis. The molecular weight was estimated to be about 9.6 × 10⁴ by SDS-disc electrophoresis.

The enzyme showed high activities toward maltose, nigerose, phenyl-α-maltoside, and maltooligosaccharides. The ratios of maximum velocity for maltose, nigerose, kojibiose, isomaltose, phenyl-α-glucoside, phenyl-α-maltoside, panose, turanose, and soluble starch were estimated to be 100 : 78 : 17 : 11 : 28 : 100 : 31 : 3.4 : 126, and the Km values for these substrates, 1.5 mM, 1.4 mM, 0.48 mM, 14 mM, 4.2 mM, 1.1 mM, 5.0 mM, 0.28 mM and 52mg/ml, respectively. The maximum velocity for soluble starch was high, but this α-glucan was not a favorable substrate because the Km value was also very high. The V_max for maltooligosaccharides were somewhat dependent on the degree of polymerization (n). The Km values for substrates having four or more glucose units increased with the increase in n.     

Immunological relation between 14 S dynein and 30 S dynein from the cilia of Tetrahymena pyriformis.

The immunological relation between 14 S dynein and 30 S dynein obtained from Tetrahymena cilia was investigated by using antisera specific for each dynein subunit or some dynein subunits separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Although 14 and 30 S dynein main subunits have different electrophoretic mobilities, our immunodiffusion tests showed that there exists a close immunological relation between them. At least three immunologically different polypeptides designated polypeptides A, B and C are included in the 30 S dynein main band which has been recognized as a single component by electrophoresis, and that the polypeptides designated A',B' and C' are included in the 14 S dynein main bands. Polypeptides A and A',B and B', or C and C' appeared to have a certain common antigenic determinant(s). Polypeptide C of 30 S dynein was shown to possess a certain antigenic determinant(s) specific for 30 S dynein, besides the determinant common with that of polypeptide C' of 14S dynein. The second main component of 30 S dynein proved to be a specific polypeptide of 30 S dynein but not to be a degraded product of the main polypedtide. All antisera reacted with native dynein molecules to some extent, but did not inhibit dynein ATPase (ATP phosphohydrase, EC 3.6.1.3) activity significantly.     

Inhibition of Sporulation of Genus Bacillus by Various Microbial Protease Inhibitors

Several analogs modifying the 6-methoxy-2-methoxymethyl-3-(3,4-methyienedioxyphenyl)-1,4-benzodioxan-7-yl group of haedoxans were synthesized and their insecticidal activity was examined. 2-(2,6-Dimethoxyphenoxy)-1-hydroxy-6-(2-methoxy-5-methoxyethoxyphenyl)-3,7-dioxabicyclo-[3.3.0]octane, which lacked the 3-(3,4-methylenedioxybenzyloxy) moiety of the benzodioxanyl group, was not insecticidal, but caused prolonged paralysis of the housefly. A compound replacing the 6-(2-methoxy-5-methoxyethoxyphenyl) by 6-(5-butoxy-2-methoxyphenyl) exhibited insecticidal activity comparable to one thirty-thousandth of that of haedosan A. It became evident that the 1,4-benzodioxane framework charging the 3-(3,4-methylenedioxy)phenyl group is important for the insecticidal activity of haedoxans.     

Cell-Bound Serine Proteinase of Sporulating Cells of Bacillus subtilis

2-Deuterio-2-cyclohexen-l-one, 3-deuterio-2-cyclohexen-l-one and 2-methyl-2-cyclohexen-1-one were reduced by Clostridium La 1 giving a single bioconversion product resulting from reduction of the carbon-carbon double bond. Stereochemistry of the reaction was studied.