Occurrence of nicotianamine in higher plants

Nicotianamine is present in highest concentration in growing leaf tissue and has been found not only in the Solanaceae but also in the Liliaceae and Gramineae.     

Biosynthesis of azetidine-2-carboxylic acid from methionine in Nicotiana tabacum

The administration of dl-methionine-[1¹⁴C] to Nicotia tabacum resulted in the formation of radioactive azetidine-2-carboxylic acid (isolated by dilution) which was specifically labelled on its carboxyl group. This result and other evidence strongly indicates that this imino acid is a normal component of tobacco.     

Biosynthesis of azetidine-2-carboxylic acid in Convallaria majalis

Convallaria majalis plants were fed dl-methionine-[1-¹⁴C]. [1-¹⁴C, 4-³H], and [1-¹⁴C, 2-³H], S-adenosyl-l-methionine-[1-¹⁴C], and dl-homoserine-[1-¹⁴C], resulting in the formation of labeled azetidine-2-carboxylic acid (A-2-C). The complete retention of tritium relative to carbon-14 in the feeding experiment involving methionine-[1-¹⁴C, 4-³H] indicates that aspartic acid or aspartic-β-semialdehyde are not intermediates between methionine and A-2-C. However, since the A-2-C derived from methionine-[1-¹⁴C, 2-³H] had lost 95% of the tritium relative to the C-14, it is not considered that methionine or its S-adenosyl derivative are the immediate precursors of A-2-C. Our data and that of others is consistent with the intermediate formation of γ-amino-α-ketobutyric acid which on cyclization yields 1-azetine-2-carboxylic acid, A-2-C then being formed on reduction.     

Resistance to (L)-azetidin-2-carboxylic acid in Bacillus subtilis.

A spontaneous mutant of $\text{Bacillus subtilis}$ resistant to (L)-azetidin-2-carboxylic acid, a structural analogue of (L)-proline, has been isolated and characterized. Data have been obtained which indicate that $\text{in vitro}$ binding of [¹⁴C]-proline to tRNAs from the resistant strain is reduced only in part by (L)-azetidin-2-carboxylic acid, while a complete inhibition of binding occurs using tRNAs from parental strain. The mutation conferring resistance to the analogue and a mutation for proline auxotrophy have been mapped.     

2-amino-4-acetylaminobutyric acid, 2,4-diaminobutyric acid and 2-amino-6N-oxalylureidopropionic acid (oxalylalbizziine) in seeds of acacia angustissima

A new amino acid previously detected in 17 species of Acacia has been isolated from seeds of Acacia angustissima and identified as oxalylalbizziine. These seeds also contain more than 6% dry weight of 2-amino-4-acetylaminobutyric acid, which has not been reported previously in a legume, and lower concentrations of 2,4-diaminobutyric acid.     

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.     

Proline overproduction in cells of the green alga Nannochloris bacillaris resistant to azetidine-2-carboxylic acid

Abstract Cells of N. bacillaris have been selected that are resistant to the toxic proline analogue azetidine-2-carboxylic acid (A2C) in 7% artificial seawater (ASW). This phenotype is stable in the absence of selection pressure. A2C resistance at low salinity was demonstrated to be due to an overproduction of proline in these cells, while levels of other amino acids were unaffected. Both wild-type and A2C-resistant cells respond to growth in high salinity media (100% ASW, 200% ASW) by accumulation of proline, but proline levels at all salinities are higher in the A2C-resistant cells than in the wild-type. Proline overproduction in the A2C-resislant cells did not affect fluctuations in the levels of other salinity-dependent solutes, such as homarine. A mutant with this level of specificity over a wide range of water potentials has not been reported for other plants and algae. Both the wild-type and A2C-resistant cells were able to grow over the entire salinity range tested (7%-300% ASW). However, the A2C-resistant cells showed a lower division rate than the wild-type in 300% ASW, and yield of A2C-resislant cells was lower than yield of wild-type cells at the salinity extremes (7% ASW, 300% ASW). The response or wild-type and A2C-resistant cells to rapid increases in salinity were similar for both growth and photosynthesis. The presence of a constitutive high level of proline in the A2C-resistant cell line did not confer any obvious increased tolerance to salinity shocks, indicating that there are other important factors in the biochemical adaptation to salinity in these cells.     

Distribution of saccharopine and 2-aminoadipic acid in higher plants

Saccharopine and 2-aminoadipic acid have been identified in eleven plant species belonging to nine families. The amino acids have been isolated from green parts of the plants using ion-exchange chromatography and preparative high voltage electrophoresis, and in three cases the identification was supported by mass spectroscopy. Mild conditions were used during the isolation to avoid lactamization, and the contents of saccharopine and 2-aminoadipic acid have been determined semiquantitatively. The significance of the occurrence of the two amino acids with regard to lysine metabolism is briefly discussed.     

Stereochemistry of 2-aminopimelic acid and related amino acids in three species of asplenium

We previously reported two free D-amino acids, D-2-aminopimelic acid (D-APA) and trans-3,4-dehydro-D-2-aminopimelic acid (D-Δ-APA), from Asplenium unilaterale. In the present work we isolated 4-hydroxy-2-aminopimelic acid (OH-APA) from the same plant and determined it to be the α-L-form. We also investigated the configurations of these amino acids isolated from A. prolongatum and A. wilfordii which are morphologically distinct from A. unilaterale. In A. prolongatum, APA was the D- and OH-APA was the L-isomer. In contrast, APA from A. wilfordii was partially racemized and the degree of racemization was significantly different in plant material collected in July and November, L:D = 3:2 and 3:7, respectively. In A. wilfordii OH-APA was almost pure L- and Δ-APA was mostly the D-isomer.     

Changes in the free and total amino acid composition of ripening chestnut seeds

The distribution of free and protein amino acids during seed development is described for three chestnut varieties. Asparagine accumulation was shown to correlate with protein biosynthesis. Accumulation of free amino acids takes place before that of proteins in ripening seeds. A temporary decrease was generally accompanied by protein biosynthesis and followed by final accumulation of both protein and free amino acids.     

Saccharopine and 2-aminoadipic acid in Reseda odorata

2(S),2′(S)-N⁶-(2′-Glutaryl)lysine (l-saccharopine) and 2(S)-2-aminoadipic acid have been isolated from Reseda odorata. When traditional isolation procedures are used l-pyrosaccharopine (5(S),5′(S)-N-(5′-amino-5′-carboxy-pentyl)-2-pyrrolidone-5-carboxylic acid) is formed from l-saccharopine by lactamisation. The degree of lactamisation during various isolation steps has been studied, The amino acids were identified by IR and PMR spectroscopy and the configurations established by enzymic and polarimetric analyses. The contents of saccharopine and 2-amino-adipic acid have been determined relative to the total nitrogen content at various stages in the growth cycle of R. odorata.     

A growth inhibitor, 2-thioxothiazolidine-4-carboxylic acid from sakurajima radish seedlings

A new growth inhibitor isolated from an acetone extract of light-exposed seedlings of Sakurajima radish, was characterized as 2-thioxothiazolidine-4-ca     

Synthesis of α- and β-N-oxalyl-l-α,β-diaminopropionic acids and their isolation from seeds of Lathyrus sativus

The α- and β-N-oxalyl derivatives of l-α,β-diaminopropionic acid have been chemically synthesized and also isolated from seed extracts of Lathyrus sativus. Chemical and physical properties of the natural and synthetic isomers were in good agreement. The toxicity of the α-isomer to chicks was evaluated and compared with that of the β-isomer.     

Discovery and development of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives as Bcl-2/Mcl-1 inhibitors

Bcl-2 family proteins play a vital role for cancer cell in escaping apoptosis, and small-molecule anti-apoptotic Bcl-2 protein inhibitors have been developed as new anticancer therapies. In current study, a series of substituted 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives were developed based on the lead compound 1 (K_i = 5.2 µM against Bcl-2 protein). The fluorescence polarization assays suggested that active compounds possessed potent binding affinities to both Bcl-2 and Mcl-1 protein, but had minor or no binding affinities to Bcl-X_L protein. MTT assays showed that these compounds had certain anti-proliferative activities against cancer cells. Furthermore, it was found that active compound 11t could induce cell apoptosis and caspase-3 activation in a dose-dependent manner in Jurkat cells.     

Stimulation of insulin biosynthesis in isolated mouse islets by L-leucine, 2-aminonorbornane-2-carboxylic acid and α-ketoisocaproic acid

An immune binding technique was used for measuring the effects of certain amino acids on the rate of insulin biosynthesis. [³H]phenylalanine served as the radioactive precursor for insulin synthesized by isolated mouse pancreatic islets. L-Leucine was found to stimulate the insulin biosynthesis and this effect was observed already at a physiologic concentration in contrast to the much higher concentrations needed to stimulate insulin secretion in vitro. Furthermore, it was found that 2-aminonorbornane-2-carboxylic acid and α-ketoisocaproic acid shared with glucose and L-leucine the ability to stimulate insulin biosynthesis. In contrast, L-alanine, L-arginine and D-leucine had no stimulatory effect in the absence of glucose, while in the presence of 5 mM glucose L-arginine decreased and L-alanine increased the incorporation rate of tritiated phenylalanine. The fact that many of those compounds which stimulated insulin biosynthesis have also been shown elsewhere to be metabolized by the B-cells supports the view that the rate of insulin biosynthesis may be substrate dependent.     

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.     

In vivo formation of 1-malonylaminocyclopropane-1-carboxylic acid and its relationship to ethylene production in cocklebur seed segments: A tracer study with 1-amino-2-ethylcyclopropane-1-carboxylic acid

The in vivo formation of 1-malonylaminocyclopropane-1-carboxylic acid (malonyl-ACC) and its relationship to ethylene production in the axial tissue of cocklebur (Xanthium pennsylvanicum) seeds were investigated using the stereoisomers of the 2-ethyl derivative of ACC (AEC), as tracers of ACC. Of the four AEC isomers, the (1R, 2S)-isomer was converted most effectively to a malonyl conjugate as well as to 1-butene. Malonyl-AEC, once formed, was not decomposed, supporting the view that malonyl-ACC does not liberate free ACC for ethylene production in this tissue. d-Phenylalanine inhibited the formation of malonyl-AEC and, at the same time, promoted the evolution of 1-butene, whereas l-phenylalanine did not. Possibly, the d-amino-acid-stimulated ethylene production in cocklebur seed tissues is due to an increase in the amount of ACC available for ethylene production which results from the decrease of ACC malonylation in the tissues treated with d-amino acid. 2-Aminoisobutyric acid, a competitive inhibitor of ACC-ethylene conversion, did not affect the malonylation of AEC.     

Coumarin-3-carboxylic acid derivatives as potentiators and inhibitors of recombinant and native N-methyl-d-aspartate receptors

N-Methyl-d-aspartate receptors (NMDARs) are known to be involved in a range of neurological and neurodegenerative disorders and consequently the development of compounds that modulate the function of these receptors has been the subject of intense interest. We have recently reported that 6-bromocoumarin-3-carboxylic acid (UBP608) is a negative allosteric modulator with weak selectivity for GluN2A-containing NMDARs. In the present study, a series of commercially available and newly synthesized coumarin derivatives have been evaluated in a structure-activity relationship (SAR) study as modulators of recombinant NMDAR activity. The main conclusions from this SAR study were that substituents as large as iodo were accommodated at the 6-position and that 6,8-dibromo or 6,8-diiodo substitution of the coumarin ring enhanced the inhibitory activity at NMDARs. These coumarin derivatives are therefore excellent starting points for the development of more potent and GluN2 subunit selective inhibitors, which may have application in the treatment of a range of neurological disorders such as neuropathic pain, epilepsy and depression. Surprisingly, 4-methyl substitution of UBP608 to give UBP714, led to conversion of the inhibitory activity of UBP608 into potentiating activity at recombinant GluN1/GluN2 receptors. UBP714 also enhanced NMDAR mediated field EPSPs in the CA1 region of the hippocampus. UBP714 is therefore a novel template for the development of potent and subunit selective NMDAR potentiators that may have therapeutic applicability in the treatment of patients with cognitive deficits or schizophrenia.