Tetrahydrofolic acid: An inhibitor of the methyltetrahydrofolic acid-mediated methylation of indolethylamines

Tetrahydrofolic acid exerts a product inhibition on the methyltetrahydrofolic acid-mediated methylation of indolethylamines. Kinetic studies showed that this inhibition was competitive with respect to methyltetrahydrofolic acid and non-competitive with respect to N-methylserotonin. Chromatographic separation of S-adenosylmethioniee-dependent indolethylamine N-methyltransferase and methyltetrahydrofolic acid-dependent methyltransferase from rabbit lung was obtained. There was no cross reaction of the two enzymes to tetrahydrofolic acid, S-adenosylhomocysteine, N,N-dimethyltryptamine or bufotenin.     

Novel Types of Spin Labelled Nucleoside Analogues

Abstract

A variety of modified nucleosides or dinucleosides bearing one of the following functions have been prepared: N-hydroxyureas, N-hydroxyamines, N-hydroxycarbamates, α-(N-hydroxyamino)phosphonates. Upon oxidation, these compounds afford the corresponding aminoxyl free radicals which have been studied by EPR spectroscopy. Some of these compounds exhibited antiviral properties.     

Interspecific transformation and DNA characteristics in Allomyces

Summary Heterologous deoxyribonucleic acid treatment in Allomyces has been shown to transfer epigynous versus hypogynous character in the recipient species.A certain proportion of inverted sexual arrangements have been consistently detected in the acceptors.The uptake of native DNA was demonstrated using labelled ³²P-nucleic acid. The uptake was found to be higher in homologous (controls) than heterologous receptors.Chromatographic fractionation of the total DNA reveals 3 types differing in their Tm values and therefore GC ratios; these appear to be localized in nuclei, mitochondria and residual cytoplasm.     

Synthesis of Some O,O-Dialkyl N-[4-(N-heteroarylsulfamoyl)-phenyl]phosphoramidothioates as Potential Fungicides

Fourteen new O, O-dialkyl N-[4-(N-heteroarylsulfamoyl)phosphoramidothioate having thiazoles and oxadiazoles as heteroaryl moieties have been synthesised. They have been tested against two species of fungi and their fungicidal activities have been compared with those of two commercial fungicides, viz., Dithane M-45 and Bavistin.     

Synthesis and bioactivity of chemotactic tetrapeptides: fMLF-OMe analogues incorporating spacer aminoacids at the lateral positions

A small library of N-For and N-Boc tetrapeptidic analogues of the chemotactic tripeptide For-Met-Leu-Phe-OMe (fMLF-OMe), obtained by incorporating three different spacer aminoacids (Gly, βAla and Pro) between the native residues of Met and Leu (N-For- and N-Boc-Met-Xaa-Leu-Phe-OMe; Xaa² series) and Leu and Phe (N-For- and N-Boc-Met-Leu-Xaa-Phe-OMe; Xaa³ series), have been synthesized and examined for their biological activity as agonists and antagonists. Chemotaxis, lysozyme release and superoxide anion production have been measured. All the N-For analogues maintain good to moderate chemotactic activity with the βAla³ 15 model reaching the maximum value. All the N-Boc tetrapeptides are efficient chemotactic antagonists. Conversely, with the exception of the moderate antagonistic activity exhibited by the N-Boc Xaa² models against lysozyme release, all the other N-Boc analogues do not show significant activity against both superoxide anion and lysozyme release.     

Antimicrobial activities of someN-alkylmaleimides

Summary A variety ofN-alkylmaleimides have been prepared and screened for antimicrobial activity using various fungi, yeasts and bacteria.N-Methyl,N-octyl andN-decylmaleimide showed antifungal activities. All test compounds showed antibacterial activity.     

Kerr constants of amides and peptides

Molar Kerr contants _mK have been determined for N-methylacetamide, N-ethyl-acatamide, N-methylpropionamide, N-acetylglycine-N′-methylamide, N-acetyl-L -ala-nine-N′-methylamide, and N-acetyl-L -leucine-N′-methylamide from electric birefringence measurements on dilute solutions in dioxane. The resultes are compared with configurational averatges 〈_mK〉 calculated on the basis of conformational energies. Values of_mK calculated for various fixed confromations on the peptides vary over a wide range depending on the choice of conformation; hece, the configurational averages 〈_mK〉 are sensitive to smalll changes in the conformational enerey. Kerr constants are calculated for random coiled oligoglycine and oligoalanine peptides as functions of chain length. The Kerr constant is an especially acute index of the average conformation.     

Synthesis and Herbicidal Activity of Pyridinyloxyphenoxypropionamides

New derivatives of pyridinyloxyphenoxypropionamide were synthesized, which have an unnatural α-amino acid or its decarboxylated structure as amide moieties. Some compounds such as N-(1-metboxycarbonyl-l-tert-butylamino)methyl, N-methoxymethyl and N-hydroxymethyl 2-[4-(3-chloro-5-trifluoromethyl-2-pyridinyloxy)phenoxy] propionamide were found to show stronger herbicidal activity against grass weeds than that of pyridinyloxyphenoxypropionamides which have already been synthesized.     

The production of biopharmaceuticals in plant systems

Biopharmaceuticals present the fastest growing segment in the pharmaceutical industry, with an ever widening scope of applications. Whole plants as well as contained plant cell culture systems are being explored for their potential as cheap, safe, and scalable production hosts. The first plant-derived biopharmaceuticals have now reached the clinic. Many biopharmaceuticals are glycoproteins; as the Golgi N-glycosylation machinery of plants differs from the mammalian machinery, the N-glycoforms introduced on plant-produced proteins need to be taken into consideration. Potent systems have been developed to change the plant N-glycoforms to a desired or even superior form compared to the native mammalian N-glycoforms. This review describes the current status of biopharmaceutical production in plants for industrial applications. The recent advances and tools which have been utilized to generate glycoengineered plants are also summarized and compared with the relevant mammalian systems whenever applicable.     

PARTIAL CHARACTERIZATION OF BASIC PROTEINS OF CHICKEN, TURTLE AND FROG CENTRAL NERVOUS SYSTEM MYELIN

Myelin basic proteins were isolated from CNS tissues of chicken, turtle and frog and compared with the corresponding protein of bovine origin. At acid pH all four proteins had comparable mobilities in polyacrylamide gels. Upon electrophoresis at alkaline pH the submammalian proteins, like the bovine protein, were separated into multiple components. The components of the chicken and frog proteins had exceptionally high and low mobilities, respectively, while those of the turtle protein had mobilities comparable to those of the bovine protein. The chicken and turtle proteins were similar to the bovine protein in amino acid composition except for containing considerably more serine and valine and having higher proportions of histidine to lysine. The frog protein differed further in having an unusually high content of tyrosine (approx 9 mol/mol protein), an unusually high arginine: glycine ratio (1.09) and practically no methylated arginine (0-0.036 mol/mol protein). Like those of mammalian origin, the submammalian proteins each contained a single tryptophan and two methionines. Arginine, serine and glycine together accounted for approximately 40 per cent of the residues in each protein. The chicken and turfle proteins each contained roughly equal amounts of N^G-monomethyl- and N^G, N^G-dimethylarginine, the two derivatives together comprising 0.5-0.6 mol/mol protein. No N^G, N^G-dimethylarginine was detected in any of the proteins examined. The microheterogeneity observed in the chicken and turtle proteins upon electrophoresis at alkaline pH was reproduced upon alkaline pH chromatography on carboxymethylcellulose. Chromatographic fractions of the chicken protein which differed electrophoretically at alkaline pH had virtualy identical amino acid compositions and apparent molecular weights and all contained comparable amounts of both N^G-monomethyl- and N^G, N^G-dimethylarginine. Treatment of the submammalian proteins with BNPS-skatole yielded two fragments comparable in size, charge and staining characteristics to those similarly produced from the bovine protein (residues 1-116 and 117-170). Fragments produced from the frog protein by treatment with BrCN were comparable in size and charge to those similarly produced from the bovine protein; those produced from the chicken and turtle proteins were much different. In immunodiffusion studies the submammalian and bovine proteins showed reactions of identity when tested against rabbit anti-chicken basic protein serum.     

Unusual amino acids VI. Substituted arylamino acids by asymmetric hydrogenation of N-Cbz and N-Boc protected dehydroamino acid derivatives

Substituted N-Cbz and N-Boc protected arylamino acrylic acids and esters have been prepared and used in asymmetric hydrogenations catalyzed by PROPRAPHOSRh. Stereoselectivities > 90% ee could be achieved, the rate of which is dependent on the position of the substituent in the aromatic ring. The N-Boc derivatives provide advantages compared with the N-Cbz analogues. The amino acid derivatives were fully characterized by ¹⁹F, ¹³C, and ¹H NMR spectroscopy. © 1996 Wiley-Liss, Inc.     

Tumour necrosis factor-α and soluble Fas ligand as biomarkers in non-acetaminophen-induced acute liver failure

Arylamines and nitroarenes are very important intermediates in the industrial manufacture of dyes, pesticides and plastics, and are significant environmental pollutants. The metabolic steps of N-oxidation and nitroreduction to yield N-hydroxyarylamines are crucial for the toxic properties of arylamines and nitroarenes. Nitroarenes are reduced by microorganisms in the gut or by nitroreductases and aldehyde dehydrogenase in hepatocytes to nitrosoarenes and N-hydroxyarylamines. N-Hydroxyarylamines can be further metabolized to N-sulphonyloxyarylamines, N-acetoxyarylamines or N-hydroxyarylamine N-glucuronide. These highly reactive intermediates are responsible for the genotoxic and cytotoxic effects of this class of compounds. N-Hydroxyarylamines can form adducts with DNA, tissue proteins, and the blood proteins albumin and haemoglobin in a dose-dependent manner. DNA and protein adducts have been used to biomonitor humans exposed to such compounds. All these steps are dependent on enzymes, which are present in polymorphic forms. This article reviews the metabolism of arylamines and nitroarenes and the biomonitoring studies performed in animals and humans exposed to these substances.     

N-Acylphosphatidylethanolamine, a phospholipid that is rapidly metabolized during the early germination of pea seeds

1. A phospholipid that rapidly disappears from pea seeds during the early stages of germination has been isolated and shown to be N-acylphosphatidylethanolamine. 2. Chromatographic evidence for the presence of the same phospholipid in oats, soya beans and spring (tick) beans has been obtained, and its loss during early germination measured. 3. A scheme for the stepwise degradation of the phospholipid with alkali and acid is presented.     

Glycoform Analysis of N-Glycans Linked to Glycoproteins Expressed in Rice Culture Cells: Predominant Occurrence of Complex Type N-Glycans

Although it has been found that plant endo-β-N-acetylglucosaminidase shows strong activity towards denatured glycoproteins and glycopeptides with high-mannose type N-glycans and free high-mannose type N-glycans bearing the chitobiosyl unit, the endogenous substrates for plant endoglycosidase have not yet been identified. Recently we purified and characterized an endo-β-N-acetylglucosaminidase from rice culture cells and identified the gene encoded (Maeda, M., and Kimura, Y., Trends Glycosci. Glycotech., 17, 205–214 (2005)). Furthermore, we found structural features of free N-glycans in the cells, indicating that high-mannose type species (Man_9-5GlcNAc₁) occur at concentration of several micromolar (μM). Hence, in this study we analyzed glycoform of N-glycans linked to glycoproteins expressed in rice culture cells to see whether endogenous glycoproteinous substrate occurs in reasonable amounts. Structural analysis revealed that more than 95% of total N-glycans linked to glycoproteins in the rice cells had the plant complex type structure, including Lewis a epitope-harboring type, although high-mannose type structures account for less than 5% of total N-glycans.     

RNA turnover in cultured hamster embryo cells: Identification of modified nucleoside end products

Fourteen methylated nucleosides (N-2-dimethylGuo, N-2-methylGuo, N-1-methylGuo, N-5-methylUrd, N-3-methylUrd, N-1-methylAdo, N-3-methylCyd, N-5-methylCyd, N-1-methyllno, 2′-0methyl-Cyd, 2′-0-methylUrd, 2′-0-methylGuo, 2′-0-methyllno, and thymidine) and one methylated base (m⁷Gua) have been identified as normal excretion products of cultured hamster embryo cells. The methylated nucleosides are excreted in the culture media subsequent to RNA turnover. The excretion pattern of the base-methylated nucleosides was determined by continuous labeling of serum-stimulated quiescent hamster embryo cells with [³H-CH₃]methionine and measurement of radioactivity in the excreted nucleosides between 23 and 81^1/2 hours after the label was added. These nucleosides accumulate exponentially until a maximum level is reached after 60 hours. These maximum levels were maintained for at least an additional 20 hours.     

Synthesis of Some Hydroxamic Acids Related to Uridine: Potential Inhibitors of Ribonucleoside Diphosphate Reductase

Abstract

5-(N-Hydroxy) carboxamidouridine (5) and 5-(N-hydroxy) carboxamido-methyluridine (6) have been synthesized; these hydroxamic acids incorporate a radical trap into a nucleoside structure, and are designed as potential inhibitors of ribonucleotide diphosphate reductase.     

Configurational statistics of polysaccharide chains. Part III. Linear β-(1 → 4′) xylan and mannan

The characteristic ratio C_N = 〈r²〉₀/Nl_v² of the β-D (1 → 4′)-linked polysaccharides xylan and mannan has been computed as a function of the angle τ at the bridge oxygen atom and the degree of polymerization N. The calculated values of the characteristic ratio C_N are very high relative to their free rotational dimensions. The characteristic ratio of these polysaecharides converges to the asymptotic value at low degree of polymerization at higher τ values. The low values of the calculated characteristic ratio of xylan compared to cellulose and mannan for the same τ value indicate that the former is more flexible and assumes a compact configuration. A pronounced difference in the values of the characteristic ratio C_N of cellulose and mannan has also been observed lower τ angles (<120°). On the other hand, nearly the same values of C_N have been obtained at higher τ angles (120°–125°), which suggests that, cellulose and mannan may have similar configuralons in certain solvents.     

Sustained ammonia production by immobilized filaments of the nitrogen-fixing cyanobacterium Anabaena 27893

Summary Whole filaments of the N₂-fixing cyanobacterium Anabaena ATCC 27893 have been immobilized by entrapment in calcium alginate gel beads. In a continuous flow fluidized bed reactor sustained photosynthesis, N₂-fixation, and ammonia production have been achieved over a 130 hour period, the longest tested.     

Nucleophilic substitution at C-2 of S-alkylated 2-thiocytidines by cysteine and lysine : A new method for specific covalent linking of peptides to nucleic acids

S-Alkylated 2-thiocytidine can be substituted at C-2 by nucleophilic agents. This reaction has been investigated with model compounds as well as with tRNA using the amino acids cysteine and lysine in order to develop a new affinity label linking covalently tRNA and a protein. Reaction with N-protected cysteine gives 2-S-alkyl-pyrimidines, while unprotected cysteine yields an N-alkyl-pyrimidine, after intramolecular substitution. With the -amino group of lysine a fast replacement at C-2 is observed, leading to an unstable 2-N-alkyl-pyrimidine. All products have been characterized both chemically and spectroscopically.