Synthesis and gastrointestinal pharmacology of some 15- and 16- modified (±)-11-deoxyprostaglandins

The synthesis and gastrointestinal pharmacology of some 11-deoxyprostaglandin E₁ analogues are described with results analysed for selectivity from side effects. 11-Deoxygenation reduced potency relative to PGE₂ but, as has been reported for natural PGs, 15- or 16-methyl analogues were more potent than the unsubstituted parent compound in the order 16-methyl > 15-methyl > 16, 16-dimethyl. The results suggest that a complex interaction between C-15 and C-16 in methyl analogues affects their profile of activity, but that none of the modifications studied conferred a substantial potency or selectivity advantage over PGE₂.     

Sensitivity of the vibrios to ultraviolet-radiation.

The ultraviolet-inactivation kinetics of a number of strains of Vibrio cholerae (classical), Vibrio cholerae (el tor), NAG vibrios and Vibrio parahaemolyticus were investigated. Statistical analyses revealed significant differences between any two of the four types of vibrio in respect to their sensitivity to U.V.     

C nuclear magnetic resonance studies of the binding of alkyl isocyanides to soybean leghemoglobin; comparison with animal myoglobins

¹³C NMR of labelled alkyl isocyanide ligands has been used with a view to probe the protein environment around the heme site of Soybean leghemoglobin, and comparatively, those of sperm whale myoglobin and monomeric Glycera hemoglobin. The terminal carbon of the isocyanide, which is known to be highly sensitive to change in hybridization of the nitrogen, could be expected to reflect the movement of the alkyl group through steric interactions. Three alkyl isocyanides (alkyl = methyl, ethyl & n-butyl) have therefore been used and the ¹³C° chemical shift values were measured for each ligand bound to the various proteins studied.In all cases, the ¹³C° resonances of the bound ligand were shifted considerably downfield with respect to those of the free unbound species, but the pattern of these displacements revealed more pronounced steric hindrance in the case of some proteins compared to others. The modifications of the chemical shift values on binding Δδ = δ_bound — δ_free) were least in the case of leghemoglobin; moreover, the Δδ values were insensitive to the length of the alkyl chain (methyl to n-butyl) when bound to leghemoglobin, in contrast to the other proteins examined. The results are interpreted as arising from a diminished steric hindrance to isocyanide binding with leghemoglobin, in conformity with the recently published X-ray structure which reports the existence of a large heme pocket on the distal side.     

Inhibition of glycolysis by furfural in Saccharomyces cerevisiae

Summary Furfural, a Maillard reaction product, was found to inhibit growth and alcohol production by Saccharomyces cerevisiae. Furfural concentrations above 1 mg ml^–1 significantly decreased CO₂ evolution by resuspended yeast cells. Important glycolytic enzymes such as hexokinase, phosphofructokinase, triosephosphate dehydrogenase, aldolase and alcohol dehydrogenase were assayed in presence of furfural. Dehydrogenases appeared to be the most sensitive enzymes and are probably responsible for the observed inhibition of alcohol production and growth.     

Biochemical studies on the origin of the ATPase of the avian myeloblastosis virus

The adenosine triphosphatase activity of the avian myeloblastosis virus obtained from the blood of the virus-infected chicken was compared with that of the host cell myeloblasts. The specific activity of the viral enzyme is unusually higher than that of the myeloblasts. A significant difference in inhibitor sensitivity was observed with quercetin. When the virus was grown in chicken embryonic fibroblasts in culture, the resulting virus showed very little adenosine triphosphatase activity, comparable to that of the fibroblasts and similar sensitivity to inhibitors. Antibody raised against the purified enzyme of avian myeloblastosis virus inhibits the enzyme activity of the myeloblasts while the activity of the fibroblasts enzyme as well as that of fibroblast-grown virus remains unaffected.