Determination of CGTase from Bacillus ohbensis and Its Optimum pH Using HPLC

Glucose is widely known to be required during superoxide generation in phagocytic cells. However, when an specific chemiluminescence probe with the Cypridina luciferin analog 2-methyl-6-(p-methoxyphenyl)-3, 7 -dihydroimidazo[ 1,2-a]pyrazin-3-one (MCLA) was used, about 60% of the chemiluminescence remained in stimulated macrophages in the presence of the glycolytic inhibitor 2-deoxyglucose. -nonspecific luminol-dependent chemiluminescence disappeared when the same drug was added. These results clearly demonstrate that the generation of by macrophages is not completely glucose-dependent, and strongly suggest that macrophages have both glucoseindependent NADPH-supplying pathway(s) and glucose dependent pathway(s) which generate reactive oxygen species other than .     

Conformation depends on 4D-QSAR analysis using EC–GA method: pharmacophore identification and bioactivity prediction of TIBOs as non-nucleoside reverse transcriptase inhibitors

The electron conformational and genetic algorithm methods (EC–GA) were integrated for the identification of the pharmacophore group and predicting the anti HIV-1 activity of tetrahydroimidazo[4,5,1-jk][1,4]benzodiazepinone (TIBO) derivatives. To reveal the pharmacophore group, each conformation of all compounds was arranged by electron conformational matrices of congruity. Multiple comparisons of these matrices, within given tolerances for high active and low active TIBO derivatives, allow the identification of the pharmacophore group that refers to the electron conformational submatrix of activity. The effects of conformations, internal and external validation were investigated by four different models based on an ensemble of conformers and a single conformer, both with and without a test set. Model 1 using an ensemble of conformers for the training (39 compounds) and test sets (13 compounds), obtained by the optimum seven parameters, gave satisfactory results ( = 0.878, = 0.910, q² = 0.840, = 0.926 and = 0.900).     

Antitumor Protein-containing Polysaccharides from a Chinese Mushroom Fengweigu or Houbitake,Pleurotus sajor-caju (Fr.) Sings

Protein-containing polysaccharides extracted from fruiting bodies of a Chinese fungus named Feng Wei Gu, were fractionated and purified, and their antitumor activities were tested, out of which the following active fractions were obtained.

FI_o-a: A protein-containing xyloglucan, MW 280,000, polysaccharide: protein=76: 24 (w/w), polysaccharide consisting of Man: Gal: Xyl: Glc = 2: 12: 42: 42 (molar ratio). + 25.3°.

FA-2: A protein-containing mannogalactan, MW 120,000, polysaccharide: protein = 76 : 16 (w/w), consisting of Xyl : Man: Gal = 9 : 35 : 56 (molar ratio), + 98.5°.

FII-1: A Protein-containing xylan (62: 21 w/w). MW 200,000, +8.7°.

FIII-1a: A protein-containing glucoxylan (15: 71 w/w), +30.7°, MW 90,000, consisting of Glc : Xyl = 40 : 44 (molar ratio).

FIII-2a: A protein-containing xyloglucan, MW 70,000, polysaccharide: protein = 69: 3 (w /w), polysaccharide consisting of Xyl: Glc = 36 : 62 (molar ratio). + 38.6°.     

Particular interaction between pyrimethamine derivatives and quadruple mutant type dihydrofolate reductase of Plasmodium falciparum: CoMFA and quantum chemical calculations studies

Comparative molecular field analysis (CoMFA) was performed on twenty-three pyrimethamine (pyr) derivatives active against quadruple mutant type (Asn51Ile, Cys59Arg, Ser108Asn, Ile164Leu) dihydrofolate reductase of Plasmodium falcipaarum (PfDHFR). The represented CoMFA models were evaluated based on the various three different probe atoms, C_sp3 (+1), O_sp3 ( ? 1) and H (+1), resulting in the best model with combined three types of probe atoms. The statistical results were = 0.702, S_press = 0.608, = 0.980, s = 0.156, and = 0.698 which can explain steric contribution of about 50%. In addition, an understanding of particular interaction energy between inhibitor and surrounding residues in the binding pocket was performed by using MP2/6-31G(d,p) quantum chemical calculations. The obtained results clearly demonstrate that Asn108 is the cause of pyr resistance with the highest repulsive interaction energy. Therefore, CoMFA and particular interaction energy analyses can be useful for identifying the structural features of potent pyr derivatives active against quadruple mutant type PfDHFR.     

Modelling vertical transmission in vector-borne diseases with applications to Rift Valley fever

We present two ordinary differential equation models for Rift Valley fever (RVF) transmission in cattle and mosquitoes. We extend existing models for vector-borne diseases to include an asymptomatic host class and vertical transmission in vectors. We define the basic reproductive number, ₀, and analyse the existence and stability of equilibrium points. We compute sensitivity indices of ₀ and a reactivity index (that measures epidemicity) to parameters for baseline wet and dry season values. ₀ is most sensitive to the mosquito biting and death rates. The reactivity index is most sensitive to the mosquito biting rate and the infectivity of hosts to vectors. Numerical simulations show that even with low equilibrium prevalence, increases in mosquito densities through higher rainfall, in the presence of vertical transmission, can result in large epidemics. This suggests that vertical transmission is an important factor in the size and persistence of RVF epidemics.     

Effect of intravenous nitroglycerin therapy on erythrocyte antioxidant enzymes

Intravenous nitroglycerin (GTN) has been used as an anti-ischemic agent for the therapy of unstable and post-infarction angina. Nitric oxide (^?NO) and S-nitrosothiols constitute the biologically active species formed via nitroglycerin bioactivation. Increased levels of reactive oxygen species can diminish the therapeutic action of organic nitrates by scavenging donated ^?NO and oxidizing tissue thiols important in nitrate biotransformation. Studies reported here show that the red cell activity of antioxidant enzymes, catalase and glutathione peroxidase, are significantly decreased after intravenous nitroglycerin treatment. Catalase activity decreased to and after 1 and 24?hr GTN infusion, respectively. Similarly, glutathione peroxidase activity decreased to and after 1 and 24?hr GTN infusion, respectively. The reported decrease in antioxidant enzyme activities can lead to an oxidant milieu and contribute to the generation of nitrate tolerance.     

Substrate Specificity of α-Glucosidase II in Rice Seed

The substrate specificity of rice α-glucosidase II was studied. The enzyme was active especially on nigerose, phenyl-α-maltoside and maltooligosaccharides. The actions on isomaltose and phenyl-α-glucoside were weak, and on sucrose and methyl-α-glucoside, negligible. The α-glucans, such as soluble starch, amylopectin, β-limit dextrin, glycogen and amylose, were also hydrolyzed.

The ratio of the maximum velocities for hydrolyses of maltose (G₂), nigerose (N), kojibiose (K), isomaltose (I), phenyl-α-maltoside (?M) and soluble starch (SS) was estimated to be 100: 94.4: 14.2: 7.1: 89.5: 103.1 in this order, and that for hydrolyses of malto-triose (G₃), -tetraose (G₄), -pentaose (G₅), -hexaose (G₆), -heptaose (G₇), -octaose (G₈), and amyloses ( and ), 113: 113: 113: 106: 113: 100: 106: 106. The Km values for N, K, I, ?M and SS were 2.4 mm, 0.58 mm, 20 mm, 1.6 mm and 5.0 mg/ml, respectively; those for G₂, G₃, G₄, G₅, G₆, G₇, G₈, and , 2.4 mm, 2.2 mm, 2.1 mm, 1.5 mm, 1.0 mm, 1.1 mm, 0.95 mm, 1.5 mm and 1.1 mm.

Rice α-glucosidase II is considered an enzyme with a preferential activity on maltooligosaccharides.     

New Dinucleoside Phosphonate Derivatives as Prodrugs of 3′-Azido-3′-Deoxythymidine and β-L-2′,3′-Dideoxy-3′-Thiacytidine: Synthesis and Anti-HIV Properties

New phosphonate homodimers of 3′-azido-3′-deoxythymidine (AZT) and a phosphonate heterodimer of β-L-2′,3′-dideoxy-3′-thiacytidine (3TC) and AZT were synthesized. The compounds demonstrated moderate anti-HIV activity. Stability of the compounds in human blood serum was studied. A correlation between anti-HIV activity and stability was defined.     

The Chemistry of Ilexol. IV.

It has now been shown that Acetate A previously obtained by isomerizing ilexol acetate is nothing other than urs-13 (18)-en-3β-yl acetate prepared from α-amyrin, furnishing conclusive evidence for its conversion into one of the compounds of the ursane series.

Isoilexol, oxidized with chromium trioxide at room temperature, afforded a ketone named isoilexone, C₃₀H₄₈O, m.p. 194–195°, +75.90° (c, 0.527), and oxidized with the same oxidant at 70–80°, another ketone named isoilexenedione, C₃₀H₄₆O₂, m.p. 221-223°, +16.28° (c, 0.307).

Huang-Milon reduction of these ketones afforded one and the same deoxy compound named isoilexene, C₃₀H₅₀, m.p. 183–185°, +48.34° (c, 0.290), which might well be assumed to constitute a pair of optical antipodes with olean-13 (18)-ene, C₃₀H₅₀, m.p. 184-185°, ?48.50° (c, 0.545).     

Aromatic Amino Acid Residues in Japanese-radish Peroxidase a and Apoenzyme†

The nature of aromatic amino acid residues in Japanese-radish peroxidase a and the apoprotein was investigated by means of spectrophotometry and fluorospectrophotometry. The tyrosine residues in the holoenzyme were masked in the alkali-titration, giving an abnormally high value of 12.6, while they were exposed in the apoenzyme, exhibiting a value of 10.8. The difference spectra in the ultraviolet region between the holo-and apo-enzyme showed characteristic bands of tryptophan and phenylalanine as well as tyrosine. The perturbation of the aromatic amino acid residues by 50% ethyleneglycol was observed in the apoenzyme but not in the holoenzyme. The fluorophotometric experiments also revealed that the aromatic amino acid residues were in different environments in the holo- and apoenzyme. The difference between the conformation of peroxidase and that of the apoprotein was discussed.