Isolation and Identification of Lachnophyllum Lactone and Osthol as Repellents against a Sea Snail

The rates of hydrolysis of arylβ-D-xylosides (e.g. p-NO₂-phenyl-, p-Cl-phenyl-, p-CH₃-phenyl- and p-CH₃O-phenyl-β-D-xylosides) by Malbranchea β-xylosidase were investigated. The Michaelis constants, Km, were almost independent of aglycone, whereas maximum velocity, V_max, showed a marked dependence. In all hydrolysis reactions studied, the molecular activities, k₀ (V_max/e₀, where e₀ is the molar concentration of enzyme), were markedly increased by introducing both electron-withdrawing and electron-donating substituents in the para position of the phenyl ring. Between the values of log k₀and inductive sigma constants, σ, V-shaped Hammett plots were obtained. When electron-withdrawing substituents were introduced, the Hammett reaction constant, p, was +1.27, when electron-donating substituents were introduced, its value was –2.07. On enzymic hydrolysis of p-nitrophenyl- and phenyl-β-D-xyloside, the reaction products, in both cases, were found to be α-D-xylose with inversion of configuration.     

Location and State of Methionine Residues in a Papain-synthesized Plastein from a Mixture of Soybean Protein Hydrolysate and l-Methionine Ethyl Ester

With the aid of papain, a plastein was synthesized from a 1 : 10 mixture of l-methionine ethyl ester and a peptic hydrolysate of soybean protein. Dialysis of the whole reaction-product yielded a methionine-incorporated plastein (Met-plastein) as the nondialyzable fraction, its yield being 78.2% on a dry-matter basis, of the whole reaction-product. Methionine content in this Met-plastein was 7.22% on a weight basis, while its content in the material hydrolysate was only 1.25%. Carboxypeptidase A treatment of Met-plastein liberated methionine at an outstandingly rapid rate. A similar, but not so outstanding, rate was observed for the methionine liberation from Met-plastein by treatment with leucine aminopeptidase. Methyl isothiocyanate treatment and subsequent cyclization yielded a mixture of methylthiohydantoins from Met-plastein. Gas chromatographic analysis of this mixture after trimethylsilylation showed a result that methionine occupied 33.2%, on a molar basis, of the total N-terminal amino acids. Lithium borohydride reduction and 6 n hydrochloric, acid hydrolysis of Met-plastein produced monomeric aminois, and their 2,4-dinitrophenylation followed by thin-layer chromatography gave a result that methionine occupied 84.9%, on a molar basis, of the total C-terminal amino acids; the residues amounting to 14.4% of the C-terminal methionine residues remained as an ethyl eater form. The selective degradation probe employing cyanogen bromide to generate free homoserine disclosed that the occurrence of the polymeric methionine-methionine sequence was little if any in Met-plastein. Based on the above experiments as well as an evaluation of the esterase activity against l-methionine ethyl ester, a possible mechanism was discussed of the papain-catalyzed synthesis of plastein in a system containing such an ester.     

Formation Mechanism of the Free Radical Product and Its Precursor by the Reaction of Dehydro-L-ascorbic Acid with Amino Acid

During the formation of radical A (2) and its precursor (tris(2-deoxy-2-L-ascorbyl)amine, 1) by the reaction of dehydroascorbic acid (DHA) with amino acid, ascorbic acid (AsA) and the reduced red pigment (3) were newly identified, in addition to scorbamic acid (SCA) and the red pigment (4), as intermediate products. The addition of AsA to the DHA-amino acid reaction, as well as to the DHA-SCA reaction, greatly increased the formation of 3 and 1. The reaction of AsA with 4 gave rapidly 3, followed by the gradual production of 1. From these results, a reaction pathway is proposed that 3 formed by the reduction of 4 with AsA is a key intermediate and its condensation with DHA followed by reduction with AsA might produce 2 and 1.     

Inhibitory Activities of E–64 Derivatives on Papain

In order to investigate the active site of inhibition of E–64 against papain, the constituents of E-64 and their derivatives were synthesized and their activities on papain were assayed. It was consequently found trans-epoxysuccinic acid was essential for the activity. The difference of its optical activity gave no influence on the activity, but cis-form had no activity. Moreover, the structure-activity relationship of a series of the esters of trans-epoxysuccinic acid was also discussed. From these results, it was suggested that both epoxide and carbonyl group are important in the manifestation of the inhibitory action.     

Immunological Studies on Antisera of Mice Immunized with Dried or DEPC-treated Ehrlich Ascites Tumor Cells

Intracellular arylsulfatases from Klebsiella aerogenes W70 cells grown in methionine medium (M enzyme) and inorganic sulfate medium containing tyramine (T enzyme) were purified respectively by fractionation with (NH₄)₂SO₄, followed by successive chromatographies on DEAE cellulose, hydroxylapatite, Sephadex G-100 and DEAE Sephadex A-25. On polyacrylamide gel electrophoresis, the two enzymes gave single bands with the same mobilities. Molecular weights of both, determined by SDS gel electrophoresis and by Sephadex G-100 chromatography, were 47,000 and 45,000, respectively. Their activities were maximal at pH 7.5. The affinities of the enzymes (M and T enzymes) for their substrate (Km) and the maximum velocity of hydrolysis (V_max) were enhanced by addition of electron withdrawing substituents. The enzymes were inhibited by inorganic phosphate, cyanide, hydroxylamine and tyramine. The inhibition by tyramine was competitive (Ki = 1.0 × 10^?4 m). These results show that the two enzymes were identical. This was confirmed by the fact that mutant strains, which were unable to synthesize arylsulfatase when grown with methionine, could also not synthesize the enzyme when grown with tyramine.     

2-(2-Phenylmorpholin-4-yl)pyrimidin-4(3H)-ones; A new class of potent,selective and orally active glycogen synthase kinase-3β inhibitors

A series of 2-(2-phenylmorpholin-4-yl)pyrimidin-4(3H)-ones was synthesized and examined for their inhibitory activity against glycogen synthase kinase-3β (GSK-3β). We found 21, 29 and 30 to possess potent in vitro GSK-3β inhibitory activity with good in vitro PK profiles. 21 demonstrated significant decrease of tau phosphorylation after oral administration in mice and excellent PK profiles.     

6-(4-Pyridyl)pyrimidin-4(3H)-ones as CNS penetrant glycogen synthase kinase-3β inhibitors

The discovery of a series of 6-(4-pyridyl)pyrimidin-4(3H)-ones derived from a hit compound with low molecular weight and sufficient chemical space is reported. Transformation of substituents led to subnanomolar potent inhibitors with in vivo tau phoshorylation lowering activity.     

Quality Evaluation of Steel,Aluminum, and Road Material Recycled from End‐of‐Life Urban Buildings in Japan in Terms of Total Material Requirement

In this study we introduce the concept of total material requirement (TMR) to quantify the quality of materials from end‐of‐life buildings. The TMRs for the recycling of materials (urban ore TMR [UO‐TMR]) from four types of Japanese buildings ( Japanese traditional wooden structure [ JTWS], wooden frame with walls structure [ WFS ], reinforced‐concrete structure [RCS], and steel‐based structure [SS]) have been estimated and the trade‐off between the increase in function of recycled materials such as steel made from scrap and the additional inputs of energy and materials required to create the increase in function were evaluated. Steel made from scrap, aluminum made from scrap, and road material are assumed to be recycled from steel products, aluminum products, and aggregate and cement concrete in the buildings, respectively. Case study analyses were carried out to determine the effect of recycling only aboveground materials compared to recycling both aboveground and subsurface materials. Also, the effect of varying the recycling rate of wooden demolition debris is determined. The UO‐TMRs of steel made from scrap range from 4.7 kilograms per kilogram (kg/kg) to 18.2 kg/kg. Urban tailings (unrecycled components) account for the greatest proportion of the UO‐TMR of steel made from scrap, and the next largest contributor is the recycling process. In the case of aluminum made from scrap, the UO‐TMRs range from 22 to 196 kg/kg, with the contribution of urban tailings generally dominant, and the second largest contributor being on‐site demolition and shredding. The UO‐TMRs of recycled road material range from 1.04 to 1.16 kg/kg and are similar for different recycling cases and types of buildings.