Check out our New Publishers' Select for Free Articles

Amino Acids: The Forum for Amino Acid, Peptide and Protein Research (v.12, #1)

Polyaminen and brain injury by N. de Vera Ph. D.; L. Camón; E. Martínez (pp. 1-7).

The cerebral ODC/polyamine system is disturbed by brain injury. The main modifications are important increases in ODC activity and putrescine concentration, with minor variations in spermidine and spermine concentrations. A great diversity of stimuli such as cerebral ischemia or overstimulation of the central nervous system by chemical or non-chemical agents can induce polyamine disturbances. Both the contribution of polyamines to the brain damage and their involvement in the repair mechanisms triggered after brain insults have been proposed.

Keywords: Amino acids; Putrescine; Spermidine; Spermine; Brain damage; Ischemia; Convulsion

Free and bonded homoisoleucine in sclerotia of the parasitic fungusClaviceps purpurea by Dr. A. Jegorov; P. Šimek; A. Heydová; L. Cvak; J. Minář (pp. 9-19).

Homoisoleucine, an unusual amino acid recently discovered in the structure of the ergopeptine alkaloid ergogaline, was determined in the parasitic fungusClaviceps purpurea Fr. (Tul.). growing on ryeSecale cereale (L.) and in its host plant. Free homoisoleucine was detected by gas chromatography-mass spectrometry (GC-MS) in the amino acid pool of sclerotia of all fungal strains examined. Since homoisoleucine was not detected in rye, it seems that the amino acid is synthetized by the fungus. Furthermore, the ratio of leucine/homoisoleucine in the free amino acid pool of sclerotia is in good agreement with the ratio of the corresponding alkaloids α-ergokryptine/ergogaline estimated by high performance liquid chromatography (HPLC). Thus, homoisoleucine is incorporated into the ergopeptines randomly with the similar specificity as leucine.

Keywords: Amino acids; Homoisoleucine; Ergot alkaloids; Claviceps purpurea

Guanidinoethane sulphonic acid interferes with the binding of [³H]dizocilpine and neurotoxic action of AF64A by Dr. R. Liljequist (pp. 21-32).

The binding of [³H]dizocilpine [[³H]MK-801] to the N-methylD-aspartate receptor complex of well washed rat cortical membranes was reduced by guanidinoethane sulphonic acid (GES). Micromolar concentrations of GES, which were high relative to those of dizocilpine, inhibited in a concentration dependent manner the binding of [3H]dizocilpine. The inhibitory effect of GES on [3H]dizocilpine binding was slightly influenced by concentration of glutamate. The glutamate antagonist DL-2-amino-5phosphonovaleric acid blocked the effect GES at concentrations higher relative to GES. The inhibitory effect of GES was still present during spermidine-induced stimulation of [³H]dizocilpine binding. GES reduced the binding of the glycine antagonist [³H]5,7-dichlorokynurenic acid with an IC₅₀ of 530 μM.. Intraperitoneal injections of GES (0.2mmol/kg) protected against both amnesia and decrease in the choline acetyltransferase activity following local injections of the neurotoxin AF64A into the nucleus basalis magnocellularis. GES given to lesioned rats during the training period in the spatial learning task gradually improved the performance to the level of sham operated rats. It is concluded that GES interferes with the transmitter and the dizocilpine binding sites of the NMDA receptor complex and has the capacity to protect against neurotoxic brain damage.

Keywords: Amino acids; Guanidinoethane sulphonic acid; [³H]Dizocilpine; Choline acetyltransferase; [³H]Glycine; [³H]5,7-Cl-Kynurenic acid; AF64A; Learning

Protective effect of glucose-cysteine adduct on thein situ perfused rat liver by W. -B. Yao; M. Tomozawa; K. Yukihiro; Prof. T. Ubuka (pp. 33-40).

Insitu perfusion of rat liver was performed with a medium containing glucose-cysteine adduct [2-(D-gluco-pentahydroxypentyl) thiazolidine-4-carboxylic acid, glc-cys] and its effect on glutathione (GSH) and ATP levels and bile production was examined. The GSH content in the liver was maintained at the original level during perfusion with 1 mM glc-cys for 2h, while it decreased significantly in the absence of glc-cys. After 4h of perfusion without glc-cys, ATP content and bile production decreased significantly besides the decrease in GSH content, but they were maintained at the original levels with glc-cys. When the perfusion was performed with the liver of rats injected with diethyl maleate (DEM), the GSH level, which was decreased to 6.0% of the control by DEM injection, was restored to 22.6% of the original level by perfusion with 2mM glc-cys for 30 min. Data indicate that glccys is a cysteine prodrug with protective action on the liver.

Keywords: Amino acids; Glucose-cysteine adduct; Cysteine prodrug; Liver perfusion; Glutathione; Diethyl maleate

Anthelmintic activity of 3,6-dibenzyl-2,5-dioxopiperazine, cyclo(L-Phe-L-Phe) by Dr. N. Walchshofer; M. E. Sarciron; F. Garnier; P. Delatour; A. F. Petavy; J. Paris (pp. 41-47).

After oral administration, dipeptide Phe-Phe-OMe1 exhibits anthelmintic activity againstEchinococcus multilocularis larvae, cestoda, in mongolian gerbils (intraperitoneal localization), but not againstHymenolepis nana, cestoda, in fasted mice (gastro-intestinal localization). This compound rapidly provides its cyclization product dioxopiperazine2 in pH 7.4 buffer at 37°C, but was stable at pH 2.4 during 16h at 30°C. It was postulated that dipeptide1 could act as a prodrug of2. Initial pharmacokinetics studies were carried out in mice and dogs. After oral administration, biotransformation of1 into2 occurred to some extent in mice but not in fasted dogs. Results of these studies did not allow to ascertain that1 is a prodrug of2. Compound2 has been tested in mice againstH. nana andSchistosoma mansoni, a gastrointestinal trematoda. Albeit less active than the reference compound praziquantel,2 has shown a good activity against both worms. 2,5dioxopiperazines represent therefore a new class of anthelmintics.

Keywords: Amino acids; 2,5-piperazine dione; Dipeptide; Anthelmintics; Hymenolepis nana ; Schistosoma mansoni ; Cyclo(Phe-Phe)

Synthesis and comparative conformational energetics of D-phenylalanylsarcosine and its cyclic dehydration product, (R)-1-methyl-3-(phenylmethyl)-2,5-piperazinedione by P. Speers; C. Chan; R. Wilcock; Prof. K. T. Douglas (pp. 49-56).

Synthetic protocols are presented both for D-PheSar and the corresponding cyclised diketopiperazine, prepared from N-t-butoxycarbonylprotected D-PheSar. Deprotection conditions could be manipulated to yield either D-Phenylalanylsarcosine or (R)-1-methyl-3-(phenylmethyl)-2,5-piperazinedione. Molecular modelling revealed several low energy conformers which contained a Z-peptide bond and which were readily amenable to cyclisation. Cyclisation was found by HPLC to be fastest in strongly acidic conditions.

Keywords: Amino acids; Diketopiperazine; Conformational analysis; Sarcosine; Acid cyclisation

Taurine transport systems in the ciliate protozoanTetrahymena pyriformis by B. Kramhøft; Dr. I. H. Lambert (pp. 57-75).

Tetrahymena pyriformis cultivated in the presence of 1 mM taurine prior to transfer of the cells to non-nutrient medium express an enhanced capacity for concentrative taurine uptake and for taurine diffusion compared to cells grown without added taurine. The unidirectional taurine influx in taurine-grown cells comprises a saturable component with K_m -257μM, V_max = 21 n-moles · g dry wt⁻¹ sd min⁻¹, and a diffusion component with a diffusion constant of 0.20 ml · g dry wt⁻¹ · min⁻¹. At extracellular taurine concentrations <30μM, 20% of the influx is via the saturable system and 80% is via the diffusion system. 19% of the influx in Na⁺-dependent, Cl⁻-independent, and not inhibitable with structural analogues to taurine, suggesting that the transport system responsible for the saturable component in Tetrahymena is different from the Na⁺- and Cl⁻-dependent taurine translocating system (theβ-system) described in vertebrate cells. The unidirectional taurine influx is reduced by 80% by 1mM DIDS (inhibitor of anion exchange and anion channels) and by 1 mM MK196 (indachrinone, inhibitor of anion channels) indicating that taurine diffusion inTetrahymena is via a channel, which is permanently active and which resembles the swelling-induced “taurine channel” seen in mammalian cells. Taurine influx is stimulated by the forskolin analogue 1,9-dideoxyforskolin and by arachidonic acid, and this stimulation is in both cases sensitive to DIDS and MK196.

Keywords: Amino acids; Taurine channels; Arachidonic acid; DIDS -1,9-Dideoxyforskolin; Indachrinone

L-tryptophan binding to hepatic nuclei: Age and species differences by H. Sidransky M. D.; E. Verney (pp. 77-84).

The present experiments report differences in in vitro nuclear binding affinity for L-tryptophan 1) between livers of young (6 1/2 weeks old) and older (30 weeks old) NZBWF₁ mice, but not so in similar aged Swiss mice, and also, 2) in livers of hamsters compared to livers of guinea pigs. In vitro hepatic nuclear specific binding affinity after tube-feeding L-tryptophan (520mg/100g body weight) to mice 1 h before killing revealed less in young than in older NZWBF₁ mice, comparable to the above in vitro assay studies. In vitro nuclear binding affinity for L-tryptophan of livers of hamsters was significantly less than that of livers of guinea pigs or Swiss mice. In general, the degree of stimulatory effect on hepatic protein synthesis, as measured by in vitro [¹⁴C]leucine incorporation into protein using microsomes of animals tube-fed L-tryptophan 1 h before killing compared to that of animals tubefed water, correlated with the basal nuclear specific binding affinity to L-tryptophan of the animals (ages and species) used.

Keywords: Amino acids; L-tryptophan; Hepatic nuclear binding; Age differences; Mice; Hamsters; Guinea pigs

Effect of glucose-cysteine adduct as a cysteine prodrug in rats by W. -B. Yao; T. Abe; Y. Kurozumi; K. Yukihiro; M. Tomozawa; Prof. T. Ubuka (pp. 85-94).

Effect of intraperitoneal administration (5 mmol/kg of body weight) of glucose- cysteine adduct (glc-cys) as a cysteine prodrug in rat tissues was studied. Cysteine levels in liver and kidney increased to 1.08 and 1.98μmol per g or ml, respectively, at 2h after the administration. GSH levels did not change substantially. However, when glc-cys was injected to rats treated with diethyl maleate, a GSH-depleting agent, the decreased GSH levels were restored rapidly. The recoveries in liver and kidney were 72% at 1h and 66% at 2h, respectively, after glc-cys administration. Metabolism of glc-cys was assessed by urinary excretion of glc-cys, sulfate and taurine. Average excretion of glc-cys was 2.86mmol/kg/24h after glc-cys administration. Increased excretions of sulfate and taurine were 0.77 and 0.14mmol/kg/24h, respectively. Data show that, although glc-cys excretion was relatively rapid, glc-cys was effectively utilized for GSH synthesis in GSH-depleted tissues.

Keywords: Amino acids; Glucose-cysteine adduct; Cysteine prodrug; Glutathione; Cysteine; Sulfate

Brain D-serine and tyrosine levels in ataxic mutant mice by Dr. Y. Nagata; R. Shoji; S. Yonezawa; S. Oda (pp. 95-100).

Since D-serine occurs at high concentrations in mammalian forebrains, the brain D-serine content was analyzed in hyperkinetic and ataxic mutant mice as well as normal control mice in a search for a physiological role. The concentrations of free D-serine (nmol/g wet weight) were 392 ± 114 (mean ± S.D.), 43 ± 17 and 18 ± 8.4 in the cerebrum, brain stem and cerebellum of the BUS mouse, respectively; and 336 ± 93,58 ± 11 and 18 ± 8.5 in the cerebrum, brain stem and cerebellum of the Rolling mouse, respectively. These values were not significantly different from those for each control animal. The present results suggest that brain D-serine may not be a cause of the abnormal movements of the mutant mice. On the contrary, among many amino acids examined, tyrosine level was found to be lower in the brain stem of BUS mouse compared to the normal control animal by amino acid analysis.

Keywords: Amino acids; D-Serine; Tyrosine; Brain; Ataxia; Mutant mouse

Phosphonic acid analogue of forfenicine — synthesis, antibacterial activity and degradation byPseudomonas fluorescens by A. Czerwonka; Prof. B. Lejczak; B. Boduszek; P. Kafarski (pp. 101-106).

Phosphonic acid analogue of forfenicine, amino (p-formylbenzyl)-phosphonic acid, was synthesized and evaluated as antibacterial agent. As indicated by disc diffusion test this compound was found to inhibit significantly the growth ofBacillus subtilis andStaphylococcus aureus and moderately the growth ofEscherichia coli. Resistance ofPseudomonas fluorescens to the action of the aminophosphonate may result from the ability of the strain to degrade this compound.

Keywords: Amino acid analogue; Phosphorus-to-carbon bond breakage; Biodegradation; Antibiotic

Sections

Personal tools

Amino Acids: The Forum for Amino Acid, Peptide and Protein Research (v.12, #1)

Sections

Personal tools

Local resources

Amino Acids: The Forum for Amino Acid, Peptide and Protein Research (v.12, #1)