New isoxazolinone amino acids from Lathyrus odoratus seedlings

In addition to β-(isoxazolin-5-one-2-yl)-alanine (I) and β-(2-β-D-glucopyranosyl-isoxazolin-5-one-4-yl)-alanine (III), previously found in Pisum sativum seedlings, two new amino acids and an amine containing the same heterocyclic ring have been isolated from Lathyrus odoratus seedlings. Their structures were determined as α-amino-γ-(isoxazolin-5-one-2-yl)-butyric acid (VI), 2-aminoethyl-isoxazolin-5-one (VII) and the γ-glutamyl derivative of the latter (V).     

Free amino acids and γ-glutamyl peptides in fagaceae

Amino acids have been investigated in seeds and fresh parts of members of the Fagaceae. Seeds from the genus Fagus contain willardiine, 5-hydroxy-6-methylpipecolic acids, N-[N-(3-amino-3-carboxypropyl)-3-amino-3-carboxypropyl]azetidine-2-carboxylic acid and γ-glutamyl peptides, mainly γ-glutamylphenylalanine. These compounds are nearly or totally absent from leaves of F. silvatica and from seedlings and immature seeds of F. silvatica var. purpurea; instead, the seedlings contain large amounts of γ-l-glutamyl-l-isoleucine and γ-l-glutamyl-l-leucine. γ-l-Glutamyl-l-tryptophan and γ-l-glutamyl-γ-l-glutamyl-l-phenylalanine, not previously known from nature, have been isolated from seeds of F. silvatica var. purpurea. The structures have been confirmed by syntheses. 4-Hydroxypipecolic acid (with trans-configuration) has been identified in seeds of F. japonica Maxim. and F. sieboldii Endl. None of the above compounds was found in Quercus or Castanea species whereas argininosuccinic acid was identified in Castanea sativa.     

N alpha-arylsulfonyl-omega-amidinophenyl-alpha-aminoalkyl-carboxylic acid amides as specific thrombin inhibitors

Structure-activity relationships for the inhibition of thrombin and trypsin by N alpha-substituted amidinophenyl-alpha-aminoalkylcarboxylic acid amides are presented. Secondary cyclic amides of N alpha-substituted 4-amidinophenylalanine and 2-amino-5-(4-amidinophenyl)valeric acid were found to be potent and specific inhibitors of thrombin, whereas trypsin was inhibited strongly by primary amides of 2-amino-4-(4-amidinophenyl) butyric acid. For this type of inhibitor the carbon amide structure seems to play a decisive role in the enzyme-inhibitor interaction.     

3-[2-Amino-2-imidazolin-4(5)-yl]alanine (enduracididine) and 2-[2-amino-2-imidazolin-4(5)-yl] acetic acid in seeds of Lonchocarpus sericeus

3-[2-Amino-2-imidazolin-4(5)-yl]alanine (enduracididine) and 2-[2-amino-2-imidazolin-4(5)-yl] acetic acid have been isolated from seeds of Lonchocarpus sericeus. The concentration of each compound was ca 0.5 % of the fresh seed weight.     

Azetidine-2-carboxylic acid derivatives from seeds of Fagus silvatica L. and a revised structure for nicotianamine

2(S),3′(S)-N-(3-Amino-3-carboxypropyl)azetidine-2-carboxylic acid and 2(S),3′(S),3″(S)-N-[N-(3-amino-3-carboxypropyl)-3-amino-3-carboxypropyl]azetidine-2-carboxylic acid have been isolated from seeds of Fagus silvatica L. (beechnuts). The structures have been established by PMR- and ¹³C-NMR-spectroscopy and by synthesis from l-azetidine-2-carboxylic acid. The second of the new amino acids is identical with nicotianamine. previously isolated from Nicotiana tabacum but assigned a different formula. The ring opening reactions of azetidine-2-carboxylic acid in neutral solution have been studied and the chemical and possibly biochemical precursor role of this amino acid for various amino acids including the two new ones described here, nicotianine [N-(3-amino-3-carboxypropyl)nicotinic acid] and methionine is discussed.     

Acide 2(R)-amino-3-butenoique (vinylglycine) dans les carpophores de Rhodophyllus nidorosus

2(R)-amino-3-butenoic acid (vinylglycine), the simplest β,γ-unsaturated α-amino acid, has been isolated from the mushroom Rhodophyllus nidorosus (Fr.) Quél. The amino acid occurs as partly racemized d-form. The structure has been confirmed by comparison with synthetic material.     

On the phosphate linkages and the structure of a disaccharide unit of the type-specific polysaccharide of pneumococcus type XIX

The structure of the capsular polysaccharide (S-XIX) of Pneumococcus Type XIX, which contains residues of d-glucose, l-rhamnose, 2-acetamido-2-deoxy- d-mannose, and phosphate, has been investigated by acid hydrolysis, treatment with acid phosphatase, mass spectrometry, and ¹³C-n.m.r. spectroscopy. Phosphoric esters in S-XIX were largely resistant to hydrolysis (4M HCl, 100°, 3 h). With M or 2M HCl at 100° for 3 h, 4-O-(2-amino-2-deoxy-β-d-mannopyranosyl)-d-glucose 4′-phosphate was liberated. More-drastic hydrolysis of S-XIX gave 2-amino-2-deoxy-d-mannose 3-, 4-, and 6-phosphates, and 4-O-(2-amino-2-deoxy-d-mannopyranosyl)-d-glucose and its 4′-phosphate.     

An Increase in Cerebral γ-Amino Butyric Acid Concentration in Children with Mild Traumatic Brain Injury in the Acute Phase: 1H MRS Study

Biophysics - In this study, the concentrations of major inhibitory (γ-amino butyric acid) and excitatory (glutamate) neurotransmitters have been estimated for the first time in the norman...     

Inhibition of Escherichia coli glutamine synthetase by phosphinothricin

The inhibition of Escherichia coli glutamine synthetase by phosphinothricin [2-amino-4-(methylphosphinyl)butanoic acid] has been studied. This amino acid was observed to function as an active site directed inhibitor exhibiting time-dependent inhibition of glutamine synthetase in the presence of ATP or adenylylimidodiphosphate (AMPPNP) but not adenylyl(β,γ-methylene) diphosphonate (AMPPCP). The inactivation was observed to be pseudo-first order. Phosphinothricin was also found to inhibit the enzyme reversibly under initial rate conditions and was competitive with respect to glutamate with K_1S = 18 ± 3 μm. The inactive enzyme inhibitor complex was found to contain approximately 11 molecules of ADP and of ³²P per dodecamer using [γ-³²P]ATP. Reactivation of the inactive enzyme complex was achieved by incubating the enzyme complex in 50 mm acetate (pH 4.4), 1 m KCl, and 0.40 m (NH₄)₂SO₄. ADP, phosphinothricin, and P_i were released upon reactivation.     

Studies on Kojic Acid and its Related γ-Pyrone Compounds

The reactions of kojic acid and its related γ-pyrones with anhydrous hydrazine have been investigated. Kojic acid and hydrazine gave 3,6-dihydroxy methyl-4-охо-1,4-dihydro- pyridazine and 3-hydroxymethyl-pyrazolyl-(5)-glycoloyl-hydrazone, respectively, in 65% and 21% yields. The same reaction occured in the case of allomaltol and pyromeconic acid and gave the analogous results. On the other hand, 5-methoxykojic acid was allowed to react with hydrazine and afforded 1-amino-2-hydroxymethyl-5-methoxy-γ-pyridone and α[3-hydroxymethyl-pyrazolyl-(5)]-α-methoxy-acetaldehyde-hydrazone, respectively. The structural elucidation of these products could be fully substantiated by chemical evidences and spectroscopic data. The mechanisms for the reactions are also discussed.     

Design and synthesis of BACE1 inhibitors containing a novel norstatine derivative (2R,3R)-3-amino-2-hydroxy-4-(phenylthio)butyric acid

A novel norstatine derivative, phenylthionorstatine [(2R,3R)-3-amino-2-hydroxy-4-(phenylthio)butyric acid; Ptns], containing a hydroxymethylcarbonyl (HMC) isostere was designed, synthesized, and stereochemically determined. Then, Ptns was introduced into the structure of BACE1 inhibitors at the P(1) position. Finally, Ptns was found as a suitable P(1) moiety for potent BACE1 inhibitor design.     

Isoxazolin-5-one derivatives in Lathyrus odoratus during development and growth

Variations in the concentrations of isoxazolin-5-ones and of some non-protein amino acids in the dry seeds, seedlings and various parts of mature Lathyrus odoratus plants were examined. The lathyrogenic compounds α-amino-γ-(isoxazolin-5-on-2-yl)-butyric acid, 2-cyanoethyl-isoxazolin -5-one and γ-glutamyl-β-aminopropionitrile were major products during development and growth.     

Free amino acids and γ-glutamyl peptides in seeds of Fagus silvatica

The contents of amino acids and peptides have been investigated in seeds of Fagus silvatica L. (beechnuts). In addition to the common amino acids, the following compounds have been isolated and identified: 4-hydroxyproline (probably the cis-l-isomer), N⁵-acetylornithine, 3-(2-furoyl)-l-alanine, methionine sulfoxide (probably an artefact), pipecolic acid (probably partially racemized d-isomer), l-willardiine (with a small amount of the d-isomer), N-(3-amino-3-carboxypropyl)azetidine-2-carboxylic acid, N-[N-(3-amino-3-carboxypropyl)-3-amino-3-carboxypropyl]azetidine-2-carboxylic acid, 2(S),5(S),6(S)-5-hydroxy-6-methylpipecolic acid, 2(S),5(R),6(S)-5-hydroxy-6-methylpipecolic acid, γ-glutamylalanine, γ-glutamylglutamic acid, γ-glutamylisoleucine, γ-glutamylleucine, γ-glutamylmethionine sulfoxide (probably an artefact), γ-glutamylphenylalanine, γ-glutamyltyrosine, γ-glutamylvaline, glutathione, γ-glutamylwillardiine, and γ-glutamylphenylalanylwillardiine. γ-Glutamylphenylalanine and willardiine are the dominating components of the amino acid fraction.The isolations were performed by use of ion exchange chromatography, taking advantage of the different pK-values of the amino acids, mainly on acid resins in the 3-chloropyridinium form with aq. 3-chloropyridine as eluant and on basic resins in the acetate form with aqueous acetic acid as eluant. These methods in combination with preparative paper chromatography have permitted the isolation and identification of compounds present in amounts as low as 1/6000 of the dominant ninhydrin-reactive component. The implications of the occurrence of this large variety of compounds in the Fagaceae are briefly discussed.     

Tetrahydrolathyrine: A new amino acid from seeds of Lonchocarpus costaricensis

A new non-protein amino acid, tetrahydrolathyrine (2(S)-3(2-amino-1,4,5,6- tetrahydropyrimidin-4-yl)alanine), has been isolated from seeds of Lonchocarpus costaricensis.     

Two carboxy- and two hydroxymethyl-substituted aristololactams from Aristolochia argentina

Four new aristololactams have been isolated from Aristolochia argentina. The evidence indicates them to be 10-amino-3-hydroxymethyl-2,4-dimethoxyphenanthrene-1-carboxylic acid lactam, 10-amino-3-hydroxymethyl-2,4,6-trimethoxyphenanthrene-1-carboxylic acid lactam, 10-amino-2-hydroxy-4-methoxyphenanthrene-1,3-dicarboxylic acid lactam and 10-amino-2-hydroxy-4,6-dimethoxyphenanthrene-1,3-dicarboxylic acid lactam.     

Convenient syntheses of phosphinic analogues of γ-aminobutyric- and glutamic acids

Three-steps, one-pot synthesis of 2-amino-4-(hydroxyphosphinyl)butyric acid from dibutyl ester of vinylphosphinic acid was carried out with an overall yield of 66%. 3-Aminopropylphosphinic acid was prepared from allylamine in three steps with an overall yield of 56%. These improved protocols allowed to obtain these commercially unavailable phosphinic analogues of glutamic acid and GABA for testing on potential molecular targets.     

Detection of an advanced glycosylation product bound to protein in situ

Protein amino groups can react with glucose without the aid of enzymes to form stable Amadori products containing 1-amino-1-deoxyketose residues. These adducts can undergo subsequent rearrangements and dehydrations to form various brown and fluorescent pigments. Recently, a chromophore, 2-(2-furoyl)-4(5)-(2-furanyl)-1H-imidazole (FFI), was isolated from acid hydrolysates of bovine serum albumin (BSA) and poly-L-lysine which had been incubated with glucose. To confirm the presence of FFI in situ, a radioimmunoassay was developed. A derivative of FFI, 4-furanyl-2-furoyl-1H-imidazole-1-hexanoic acid, was coupled to BSA and used to immunize rabbits. A radioactive FFI derivative was synthesized by reaction of 2-furyl-glyoxal with gamma-amino-[2,3-3H]butyric acid to form FFI-[3H]butyric acid. The resultant antiserum showed binding affinity to FFI and cross-reactivity for related compounds. FFI bound to proteins was liberated by acid hydrolysis or digestion by proteinase K prior to measurement. A linear relationship was seen between the amount of FFI equivalent detected and the amount of acid hydrolysate or enzymatic digest assayed. Poly-L-lysine and BSA incubated with glucose showed a time-dependent increase in the amounts of fluorescence and FFI equivalence. The detection of a time-related increase in the amount of FFI or a closely related structure in enzymatically digested proteins implicates it as an in situ product on proteins which have undergone the Maillard reaction with glucose. Of physiological significance is that FFI could also be detected in human globin and serum albumin from normal individuals. Thus, proteins exposed to glucose in vitro and in vivo form FFI as an in situ glycosylation product.     

A chlorohydrin amino acid from Amanita abrupta

A new amino acid, (2S,4Z)-2-amino-5-chloro-6-hydroxy-4-hexenoic acid, has been isolated from Amanita abrupta. Three other unusual amino acids were also isolated from the same fungus.