Analogues of geranyl pyrophosphate as inhibitors of prenyltransferase

Six analogues of geranyl pyrophosphate (the monophosphates of geraniol and tetrahydrogeraniol, and the pyrophosphates of nerol, octan-1-ol, tetrahydrogeraniol and citronellol) were synthesized, and were found to be inhibitors of pig liver prenyl- (geranyl-)transferase. The effects of each analogue were analysed in kinetic experiments, which showed the pyrophosphates of citronellol, tetrahydrogeraniol and octan-1-ol to be the most potent inhibitors. The results are interpreted to support a previous hypothesis that the main forces in the binding of substrates to prenyltransferase are non-specific lipophilic forces and a pyrophosphate-binding force.     

Effect of Externally Applied Pressure on Femoral Vein Blood Flow

The effect of incremental increases in external pressure, applied to the leg, on blood volume flow in the femoral vein was studied in dogs. Clinical investigation of external pressure increases was also carried out on nine patients undergoing surgery for varicose veins. An external pressure between 5 and 15 mm. Hg caused a sustained increase in mean femoral vein flow both in a control and in the compressed limb. Above 15 mm. Hg external pressure flow decreased in the compressed limb but was maintained at an increased level in the control limb.If external compression is to be used to prevent and treat deep vein thrombosis its application must be carefully controlled.     

Inositol Metabolism in Plants. V. Conversion of Myo-inositol to Uronic Acid and Pentose Units of Acidic Polysaccharides in Root-tips of Zea mays

The metabolism of myo-inositol-2-¹⁴C, d-glucuronate-1-¹⁴C, d-glucuronate-6-¹⁴C, and l-methionine-methyl-¹⁴C to cell wall polysaccharides was investigated in excised root-tips of 3 day old Zea mays seedlings. From myo-inositol, about one-half of incorporated label was recovered in ethanol insoluble residues. Of this label, about 90% was solubilized by treatment, first with a preparation of pectinase-EDTA, then with dilute hydrochloric acid. The only labeled constituents in these hydrolyzates were d-galacturonic acid, d-glucuronic acid, 4-O-methyl-d-glucuronic acid, d-xylose, and l-arabinose, or larger oligosaccharide fragments containing these units. Medium external to excised root-tips grown under sterile conditions in myo-inositol-2-¹⁴C contained labeled polysaccharide.     

Inositol Metabolism in Plants. IV. Biosynthesis of Apiose in Lemna and Petroselinum

The biosynthesis of apiose was investigated in cell wall polysaccharide of Lemna gibba G3 (duckweed) and in detached leaves of Petroselinum crispum (parsley). Lemna grown either in short days or in continuous light incorporated ¹⁴C from a medium containing myo-inositol-2-¹⁴C into d-apiosyl and d-xylosyl units of cell wall polysaccharides. Labeled d-apiose was characterized by paper chromatography, by formation of labeled crystalline di-O-isopropylidene d-apiose, and by gas chromatography of trimethylsilyl derivatives of apiose and of its sodium borohydride reduction product, apiitol. Periodate oxidation of labeled apiose revealed 86 to 94% of the ¹⁴C was located in formaldehyde fragments corresponding to C3′ and C4. Comparison of this result with work reported by Grisebach and Doebereiner and by Beck and Kandler supports the conclusion that myo-inositol-2-¹⁴C was converted to d-apiose labeled specifically at C4.     

Acridine Sensitivity of Bacteriophage T2H in Escherichia coli

Normally acridine-sensitive, Escherichia coli-T2H complexes are rendered acridine-resistant if the infecting bacteriophage mutant is either pr or q. If these pr or q mutants are treated to produce sensitive revertants, one obtains a mutation at any of several dye-sensitizing (ds) sites in the early enzyme region of the T2 map. The ds mutants are nonspecific suppressors because they reduce the resistance of complexes containing either pr or q to proflavine. The ds mutants are not identical in action, since some make pr or q sensitive to proflavine and quinacrine, and others, to proflavine alone. Two ds mutants have r to r(+) mutation patterns which differ, depending upon whether or not the ds is coupled with r7 (an rII mutant). The mutation patterns of r(+) to r are the same for both ds mutants and for wild type. We suggest that dye sensitization may consist of alterations of early enzymes so as to produce slightly different forms of deoxyribonucleic acid which are in turn dyesensitive.     

The action of neutral hypochlorite on epithelial mucopolysaccharides

1. The uptake of dilute neutral hypochlorite by epithelial mucopolysaccharides has been compared with that of proteins, polysaccharides, amino acids and sugars. The uptake has been shown to be related to the protein content of the mucopolysaccharides rather than their polysaccharide content. 2. The destruction of the components of epithelial mucopolysaccharides, certain sugars and polysaccharides after oxidation with dilute neutral hypochlorite at 0-4 degrees has been studied. Very little destruction of the sugar components occurred and in epithelial mucopolysaccharides the only amino acid destroyed specifically was arginine. 3. Oxidation of bovine submaxillary-gland mucoprotein and ovalbumin caused very little destruction of hexosamine and no detectable liberation of this residue as a free reducing group, indicating that the O-seryl galactosaminide and the N-acyl-glycosylamine linkages reported to be present in these compounds were relatively stable to hypochlorite. 4. Depolymerization of epithelial mucopolysaccharides by neutral hypochlorite has been studied by using gel-filtration columns and compared with the depolymerization of polysaccharides and proteins under similar conditions. The polysaccharides examined were relatively resistant to oxidation whereas the proteins were extensively broken down. It is inferred that the extensive depolymerization of epithelial mucopolysaccharides by hypochlorite is related to their protein content rather than their polysaccharide content. 5. Fractionation of the products of oxidation of epithelial mucopolysaccharides by column procedures has revealed that the relative proportions of components in all fractions were similar to those in the original material. 6. Though this study does not provide unequivocal evidence from which the overall structure of this type of epithelial mucopolysaccharide may be deduced, the balance of probabilities now appears to favour a long polypeptide chain to which a large number of oligosaccharide side chains are attached via O-seryl and O-threonyl glycosidic linkages. The results, however, are also consistent with an alternating sequence of short polysaccharide and polypeptide chains and further evidence is necessary before this structure can be ruled out.