Effect of phosphonic analogues of glutamic acid on glutamate decarboxylase

Summary Among the phosphonic analogues of glutamic acid, only 4-amino-4-phosphono butyric acid, the compound which shows the highest affinity for pyridoxal phosphate, inhibits competitively bothEscherichia coli and rat brain glutamate decarboxylases. Phosphinothricin, 2-amino-4-(methylphosphino)butyric acid, is a strong inhibitor of the mammalian enzyme.We acknowledge the gift of a sample of phosphinothricin by Prof. Przemyslaw Mastalerz as well as the technical assistance of Denois.     

Aberrant, canavanyl protein formation and the ability to tolerate or utilize L-canavanine

L-Canavanine, 2-amino-4-(guanidinooxy)butyric acid, and L-arginine incorporation into de novo synthesized proteins was compared in six organisms. Utilizing L-[guanidinooxy14C]canavanine and L-[guanidino14C]arginine at substrate saturation, the canavanine to arginine incorporation ratio was determined in de novo synthesized proteins. Caryedes brasiliensis and Sternechus tuberculatus, canavanine utilizing insects; Canavalia ensiformis, a canavanine storing plant; and to a lesser extent Heliothis virescens, a canavanine resistant insect, failed to accumulate significant canavanyl proteins. By contrast, Manduca sexta, a canavanine-sensitive insect, and Glycine max, a canavanine free plant, readily incorporated canavanine into newly synthesized proteins. This study supports the contention that the incorporation of canavanine into proteins in place of arginine contributes significantly to canavanine's antimetabolic properties.     

Aberrant,canavanyl protein formation and the ability to tolerate or utilize L-canavanine

Summary L-Canavanine, 2-amino-4-(guanidinooxy)butyric acid, and L-arginine incorporation into de novo synthesized proteins was compared in six organisms. Utilizing L-[guanidinooxy¹⁴C]canavanine and L-[guanidino¹⁴C]arginine at substrate saturation, the canavanine to arginine incorporation ratio was determined in de, novo synthesized proteins.Caryedes brasiliensis andSternechus tuberculatus, canavanine utilizing insects;Canavalia ensiformis, a canavanine storing plant; and to a lesser extentHeliothis virescens, a canavanine resistant insect, failed to accumulate significant canavanyl proteins. By contrast,Manduca sexta, a canavanine-sensitive insect, andGlycine max, a canavanine free plant, readily incorporated canavanine into newly synthesized proteins. This study supports the contention that the incorporation of canavanine into proteins in place of arginine contributes significantly to canavanine's antimetabolic properties.     

Antimutagenic unusual amino acids from plants

Five unusual amino acids were identified as antimutagens against spontaneous mutation of Salmonella typhimurium TA100: L-azetidine-2-carboxylic acid (1) from Liliaceae plants, alpha-(methylenecyclopropyl)glycine (2) from Litchi chinensis seeds, and 2-amino-4-methylhex-5-ynoic acid (3), hypoglycin A (4), and (2S,4R)-2-amino-4-hydroxyhept-6-ynoic acid (5) from Euphoria longana seeds. The absolute stereochemistry of 5 was determined by its chiral synthesis from L-allylglycine, proving that 5 is the C-4 epimer of the amino acid previously isolated from dried longan seeds.     

Studio farmacologico di un nuovo coleretico derivato dall'acidoα-cicloesil butirrico

Summary -(1-Hydroxy-4-phenyl-cyclohexyl)butyric acid (M. G. 4833) and-(1-hydroxy-3-phenyl-cyclohexyl) butyric acid (M. G. 4834) have been synthesized; both substances were endowed with choleretic activity.M. G. 4833 is the more active; it acts at lower doses and for a longer time than sodium dehydrocholate on rats, rabbits and dogs submitted to temporary fistulization of the bile-duct.     

AB型新单体及PBO树脂制备的新技术及其发展

研究以4,6-二硝基间苯二酚(DNR)和对苯二甲酸单甲酯(TAM)为原料,经三个单元过程合成AB型新单体:2-(对甲氧羰基苯基)-5-氨基-6-羟基苯并噁唑(MAB),进而均缩聚反应制备聚对苯撑苯并二噁唑(PBO)的新路线和新方法,设计了AB型新单体的产业化方案、并阐述了优于AA型单体4,6-二氨基间苯二酚(DAR)路线的特点;同时针对现有PBO技术中存在的问题,提出解决的方法和研究思路,最后对进一步发展AB型新单体:如4-(5-氨基-6-羟基-2-苯并噁唑)苯甲酸(ABA)和H2N-[PBO重复单元]-COOH结构等单体、以及高性价比PBO树脂的研究内容作了建议。     

Antimutagenic unusual amino acids from plants

Summary Five unusual amino acids were identified as antimutagens against spontaneous mutation ofSalmonella typhimurium TA100: L-azetidine-2-carboxylic acid (1) from Liliaceae plants, -(methylenecyclopropyl)glycine (2) fromLitchi chinensis seeds, and 2-amino-4-methylhex-5-ynoic acid (3), hypoglycin A (4), and (2S, 4R)-2-amino-4-hydroxyhept-6-ynoic acid (5) fromEuphoria longana seeds. The absolute stereochemistry of5 was determined by its chiral synthesis from L-allylglycine, proving that5 is the C-4 epimer of the amino acid previously isolated from dried longan seeds.This work was partly supported by a Grant-in-Aid form the Ministry of Education, Science, and Culture, Japan, No. 57740283 (to HK).     

Di- and tripeptides containing homoleucine: synthesis and biological assays on insects

Summary Some di- and tripeptides containing homoleucine (2-amino-4-methylhexanoic acid) have been synthetized. These compounds have been submitted to biological tests on insects for their hormonal activity in comparison with the known tripeptide pivaloyl-alanyl-p-aminobenzoic acid ethyl ester. Only 2 of them (3 and 4) caused morphological changes on larvae ofPyrrhocoris apterus.This work has received financial support from the Consiglio Nazionale delle Ricerche.The biological assays were done in the Research Center of Montedison S.p.A. (Linate, Milano); the collaboration of Dr G. Michièli is gratefully acknowledged.     

Zur Stereochemie der enzymatischen Dehydrierung von Butyryl-CoA

Summary The stereochemistry of the formation of crotonyl CoA from butyryl CoA catalyzed by the appropriate pig liver enzyme was investigated using samples of butyric acid specifically labelled with tritium in the two methylene groups. It is shown that oxidation involves specific removal of the pro-R hydrogen atoms from positions 2 and 3 of the substrate.     

Inhibition by tetanus and botulinum A toxin of the release of [3H]noradrenaline and [3H]GABA from rat brain homogenate

Rat brain homogenate was preloaded with [3H]noradrenaline or [3H]GABA and stimulated with high K+. Tetanus toxin and botulinum A neurotoxin partially prevent the evoked [3H]noradrenaline release in the same range of toxin concentrations starting below 10(-10) M. In contrast, release of gamma-amino butyric acid (GABA) is much more sensitive to tetanus than to botulinum A toxin.     

Effect of some phosphonic amino acids on the activity of central neurons]

Microiontophoretic applications of DL-2-amino-3-phosphonopropionic, DL-3-amino-4-phosphonobutyric, aminomethylphosphonic, 2-aminoethylphosphonic and 3-aminopropylphosphonic acids in the course of extracellular recordings of central neurons in the Rat resulted in effects which appeared similar to those observed with their carboxylic analogs. The involvement of the same post-synaptic receptors is suggested.     

Mitostatic action of 4,6-dimethyl-2-amino-3,4,5-trimethoxyphenyl-pyrimidine on mammalian cells

Summary 4, 6 dimethyl-2-amino-3, 4, 5-trimethoxyphenylpyrimidine arrests the mitotic cycle of mammalian cells in metaphase, both in vitro and in vivo. The mitostatic effect is promptly reverted by interruption of drug treatment.     

(S)-(+)-4,4,4-Trifluoro-3-(indole-3-)butyric acid,a novel fluorinated plant growth regulator

Racemic 4,4,4-trifluoro-3-(indole-3-)butyric acid (TFIBA) has been synthesized and shown to inhibitAvena coleoptile elongation. (S)-(+)-TFIBA (fig. 1), which was prepared by an enzymatic method and markedly promotes root growth of Chinese cabbage, lettuce and rice plants, is a novel fluorinated plant growth regulator. Activity of the (S)-(+)-enantiomer of TFIBA was 10-fold greater than that of the (R)-(–)-enantiomer in the first two plant species and 5-fold greater in rice.     

Free amino acid pattern in stressed leaves of two contrasting resistant and susceptible cultivars of chick pea (Cicer arietinum)

Summary Drought resistant cv. C-214 ofCicer arietinum L. showed higher accumulation of alanine, threonine, glutamine, -alanine, arginine, amino butyric acid, valine, leucine, phenylalanine than the susceptible cv. G130 under water stress.     

AMPA receptors: potential implications in development and disease

α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) receptors are one type of ionotropic glutamate receptor involved in rapid excitatory synaptic transmission. AMPA receptors have been increasingly implicated in long-term potentiation, and recent evidence suggests that they may play a role in disorders affecting the nervous system. The finding that early in postnatal development AMPA receptors are not expressed has lately been the focus of much attention. Resolving the factors involved in AMPA receptor expression suggests that their induction is a developmentally regulated process with the possibility that alterations in receptor expression may be correlated with pathology in neurological disorders. This paper provides an overview of factors involved in AMPA receptor induction as well as of their role in plasticity and neuronal pathologies. Received 5 December 2000; received after revision 12 January 2001; accepted 2 February 2001     

Inhibition by tetanus and botulinum A toxin of the release of [3H]noradrenaline and [3H]GABA from rat brain homogenate

Summary Rat brain homogenate was preloaded with [³H]noradrenaline or [³H]GABA and stimulated with high K⁺. Tetanus toxin and botulinum A neurotoxin partially prevent the evoked [³H]noradrenaline release in the same range of toxin concentrations starting below 10^–10M. In contrast, release of -amino butyric acid (GABA) is much more sensitive to tetanus than to botulinum A toxin.     

Synthese dercis-erythro- undcis-threo-Formen des Sphingosins

Summary The synthesis ofcis-erythro- andcis-threo-1, 3-dihydroxy-2-amino-4-octadecene, two further stereoisomers of sphingosine, is described.     

Intracellular trafficking of AMPA receptors in synaptic plasticity

Modification of ligand-gated receptor function at the postsynaptic domain is one of the most important mechanisms by which the efficacy of synaptic transmission in the nervous system is regulated. Traditionally, these types of modifications have been thought to be achieved mainly by altering the channel-gating properties or conductance of the receptors. However, recent evidence suggests that AMPA (α-amino-3-hydroxyl-5-methyl-4-isoxayolepropionic acid)-type ligand-gated glutamate receptors are continuously recycling between the plasma membrane and the intracellular compartments via vesicle-mediated plasma membrane insertion and clathrin-dependent endocytosis. Regulation of either receptor insertion or endocytosis results in a rapid change in the number of these receptors expressed on the plasma membrane surface and in the receptor-mediated responses, thereby playing an important role in mediating certain forms of synaptic plasticity. Thus, controlling the number of postsynaptic receptors by regulating the intracellular trafficking and plasma membrane expression of the postsynaptic receptors may be a common and important mechanism of synaptic plasticity in the mammalian central nervous system.     

Inhibition of vaccinia virus multiplication by 2-carboxymethylmercapto-4-amino-5-(p-chlorphenyl)-pyrimidine

Zusammenfassung Mit der Methode der Hemmung der Plaquebildung bei gleichzeitiger Diffusion der antiviralen Stoffe durch den Agar wurde eine hohe Selektivität des 2-Carboxymethylmercapto-4-amino-5(p-chlorphenyl)-pyrimidins für die Hemmung des Vaccinevirus festgestellt. Das Verhältnis der toxischen und der virushemmenden Konzentrationen wurde in den Membrankulturen = 15 gefunden. Die Substanz war gegen andere Viren (NDV, WEE) unwirksam.