56-88-2

Usage

Chemical Description

L-cystathionine and L-allocystathionine are amino acids that are synthesized in the experiment.

Uses

Used in Pharmaceutical Industry:
L-Cystathionine is used as an intermediate in the transsulfuration process for the conversion of methionine to cysteine, which is essential for various biological functions and the synthesis of proteins.
Used in Research and Diagnostics:
L-Cystathionine is used as a biochemical marker in ultra-performance liquid chromatography for the validation of cystathionine levels. Its abundance is correlated with vertebrate metamorphosis, making it a valuable tool in understanding biological transformations.
Used in Cancer Research:
L-Cystathionine has been utilized as an inhibitor of sinusoidal glutathione (GSH) carrier, highlighting the association between thiol redox state imbalance and the modulation of autophagy in carcinoma cells. This application aids in the study of cancer cell behavior and the development of potential therapeutic strategies.
Used in Metabolic Disorder Research:
Due to its role in the transsulfuration pathway and its expression in the mammalian brain, L-Cystathionine is used in the study and diagnosis of metabolic disorders such as cystathioninuria, which can provide insights into the underlying mechanisms and potential treatments for these conditions.

Biochem/physiol Actions

L-Cystathionine is an intermediate in the biosynthesis of L-cysteine and methionine. It is used as a substrate to differentiate and analyze cystathionine γ-lyase(s). L-Cystathionine is an important non-protein amino acid and is associated with metabolic disorders. In recent studies, L-cystathionine is believed to be the precursor of cyclic imino acid cyclothionine. Cystathioninuria is characterized with imino acid cyclothionine excretion in the urine.

Purification Methods

S,S-Cystathionine is purified by converting it to the HCl salt in 20% HCl and carefully basifying with aqueous NH3 until separation is complete. Filter it off and dry it in a vacuum. It forms prisms from H2O. The dibenzoyl derivative has m 229o (from EtOH). [IR: Greenstein & Winitz Chemistry of the Amino Acids (J Wiley) Vol 3 p2690 1961 and Tallan et al. J Biol Chem 230 707 1958, Synthesis: du Vigneaud et al. J Biol Chem 143 59 1942, Anslow et al. J Biol Chem 166 39 1946.] [Prepn: Weiss & Stekol J Am Chem Soc 73 2497 1951; see also du Vigneaud et al. J Biol Chem 143 60 1942, Biological synthesis: Greenberg Methods Enzymol 5 943 1962, Beilstein 4 IV 3197.]

InChI:InChI=1/C7H14N2O4S/c8-4(6(10)11)1-2-14-3-5(9)7(12)13/h4-5H,1-3,8-9H2,(H,10,11)(H,12,13)/t4-,5+/m1/s1

Upstream product

• 56-45-1 L-serin 
• 6027-13-0 L-homocysteine 
• 616-91-1 N-acetylcystein 
• 5809-59-6 3-cyano-3-hydroxy-1-propene 
• 143-33-9 sodium cyanide 
• 56-89-3 L-cystine 
• 59-51-8 DL-methionine 
• 672-15-1 L-homoserine 
• 5429-56-1 N-Acetamidoacrylic acid 
• 51887-89-9 β-chloro-L-alanine hydrochloride 
• 52-90-4 L-Cysteine 
• 2731-73-9 2-amino-3-chloropropanoic acid 
• 31828-68-9 L-homocysteine thiolactone hydrochloride 
• 56410-68-5 3-chloro-DL-alanine methyl ester 

Downstream Products

• 600-18-0 2-Oxobutyric acid 
• 52-90-4 L-Cysteine 
• 56-89-3 L-cystine 
• 6027-13-0 L-homocysteine 
• 127-17-3 2-oxo-propionic acid 
• 85-87-0 pyridoxamine 
• 1452573-76-0 4-[2-carboxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)-ethylsulfanyl]-2-(9H-fluoren-9-ylmethoxycarbonylamino)-butyric acid 
• 56-45-1 L-serin 
• 7664-41-7 ammonia 
• 57-60-3 piruvate 
• 339-71-9 2-keto-butyrate 
• 94862-55-2 N,N'-dibenzoyl-L,L-cystathionine 

Relevant academic research and scientific papers

NEW METHIONINE METABOLIC PATHWAY INHIBITORS

Novel compounds capable of inhibiting methionine metabolic pathway are provided. These compounds are used in inhibiting cystathionin γ-synthase (CGS) in general, and in plants, fungi and bacteria, in particular. These compounds of the invention are used as herbicides, pesticides, fungicides, agricultural plant stimulants or antimicrobial agents. The compounds of the present invention can be used for seed treatment. In particular, the compounds of the invention are used as selective herbicides, non-selective herbicides, agricultural herbicides, non-agricultural herbicides or weed killers, herbicides in integrated pest management, herbicides in gardening, herbicides in clearing waste ground, herbicides in clearing industrial or constructions sites, or herbicides in clearing railways and railway embankments.

Biogenesis of Hydrogen Sulfide and Thioethers by Cystathionine Beta-Synthase

Aims: The transsulfuration pathway enzymes cystathionine beta-synthase (CBS) and cystathionine gamma-lyase are thought to be the major source of hydrogen sulfide (H2S). In this study, we assessed the role of CBS in H2S biogenesis. Results: We show that despite discouraging enzyme kinetics of alternative H2S-producing reactions utilizing cysteine compared with the canonical condensation of serine and homocysteine, our simulations of substrate competitions at biologically relevant conditions suggest that cysteine is able to partially compete with serine on CBS, thus leading to generation of appreciable amounts of H2S. The leading H2S-producing reaction is condensation of cysteine with homocysteine, while cysteine desulfuration plays a dominant role when cysteine is more abundant than serine and homocysteine is limited. We found that the serine-to-cysteine ratio is the main determinant of CBS H2S productivity. Abundance of cysteine over serine, for example, in plasma, allowed for up to 43% of CBS activity being responsible for H2S production, while excess of serine typical for intracellular levels effectively limited such activity to less than 1.5%. CBS also produced lanthionine from serine and cysteine and a third of lanthionine coming from condensation of two cysteines contributed to the H2S pool. Innovation: Our study characterizes the H2S-producing potential of CBS under biologically relevant conditions and highlights the serine-to-cysteine ratio as the main determinant of H2S production by CBS in vivo. Conclusion: Our data clarify the function of CBS in H2S biogenesis and the role of thioethers as surrogate H2S markers.

Influence of Sulfur-Containing Diamino Acid Structure on Covalently Crosslinked Copolypeptide Hydrogels

Biologically occurring non-canonical di-α-amino acids were converted into new di-N-carboxyanhydride (di-NCA) monomers in reasonable yields with high purity. Five different di-NCAs were separately copolymerized with tert-butyl-l-glutamate NCA to obtain covalently crosslinked copolypeptides capable of forming hydrogels with varying crosslinker density. Comparison of hydrogel properties with residue structure revealed that different di-α-amino acids were not equivalent in crosslink formation. Notably, l-cystine was found to produce significantly weaker hydrogels compared to l-homocystine, l-cystathionine, and l-lanthionine, suggesting that l-cystine may be a sub-optimal choice of di-α-amino acid for preparation of copolypeptide networks. The di-α-amino acid crosslinkers also provided different chemical stability, where disulfide crosslinks were readily degraded by reduction, and thioether crosslinks were stable against reduction. This difference in response may provide a means to fine tune the reduction sensitivity of polypeptide biomaterial networks.

Synthesis and evaluation of L-cystathionine as a standard for amino acid analysis

L-Cystathionine is a key nonprotein amino acid related to metabolic conditions. The quantitative determination of L-cystathionine in physiological fluids by amino acid analysis is important for clinical diagnosis; however, certified reference material for L-cystathionine with satisfactory purity, content, and quantity has been unavailable until recently. Consequently, a practical and simple method for the preparation of L-cystathionine was examined, which involves thioalkylation of N-tert-butoxycarbonyl-Lcysteine tert-butyl ester, derived from L-cystine, with (2S)-2-(tert-butoxycarbonyl)amino-4-iodobutanoic acid tert-butyl ester, derived from L-aspartic acid, to obtain L-cystathionine with protecting groups, followed by single-step deprotection under mild conditions. This method produces L-cystathionine in high purity (99.4%) and having sufficient percentage content according to amino acid analysis, which could be used as a standard for the amino acid analysis of physiological fluids.

Detection of reaction intermediates during human cystathionine β-synthase-monitored turnover and H2S production

Human cystathionine β-synthase (CBS), a novel heme-containing pyridoxal 5′-phosphate enzyme, catalyzes the condensation of homocysteine and serine or cysteine to produce cystathionine and H2O or H 2S, respectively. The presence of he

Residue N84 of Yeast Cystathionine β-Synthase is a Determinant of Reaction Specificity

Cystathionine β-synthase (CBS) catalyzes the pyridoxal 5'-phosphate (PLP)-dependent condensation of l-serine and l-homocysteine to form l-cystathionine in the first step of the reverse transsulfuration pathway. Residue N84 of yeast CBS (yCBS), predicted to form a hydrogen bond with the hydroxyl moiety of the PLP cofactor, was mutated to alanine, aspartate and histidine. The truncated form of yCBS (ytCBS, residues 1-353) was employed in this study to eliminate any effects of the C-terminal, regulatory domain. The kcat/Kml-Ser of the N84A, N84D and N84H mutants for the β-replacement reaction is reduced by a factor of 230, 11000 and 640, respectively. Fluorescence resonance energy transfer between tryptophan residue(s) of the enzyme and the PLP cofactor, observed in the wild-type enzyme and N84A mutant, is altered in N84H and absent in N84D. PLP saturation values of 73%, 30% and 67% were observed for the alanine, aspartate and histidine mutants, respectively, compared to 98% for the wild-type enzyme. A marginal β-elimination activity was detected for N84D (kcat/Kml-Ser = 0.23 ± 0.02 M-1 s-1) and N84H (kcat/Kml-Ser = 0.34 ± 0.06 M-1 s-1), in contrast with wild-type ytCBS and the N84A mutant, which do not catalyze this reaction. The ytCBS-N84D enzyme is also inactivated upon incubation with l-serine, via an aminoacrylate-mediated mechanism. These results demonstrate that residue N84 is essential in maintaining the orientation of the pyridine ring of the PLP cofactor and the equilibrium between the open and closed conformations of the active site.

Synthesis of optically active homocysteine from methionine and its use in preparing four stereoisomers of cystathionine

In order to synthesize four stereoisomers of cystathionine (CYT), D- and L-homocysteines (D- and L-Hcy) were synthesized from methionine (Met) by a facile procedure. L-Met was reacted with dichloroacetic acid in concentrated hydrochloric acid under reflux to give (4S)-1,3-thiazane-2,4-dicarboxylic acid hydrochloride [(4S)-TDC? HCl]. L-Hcy was obtained by treatment of (4S)-TDC? HCl with hydroxylamine. D-Hcy was also synthesized from D-Met via (4R)-TDC? HCl intermediate. The obtained D- and L-Hcy were condensed with (R)- and (S)-2-amino-3-chloropropanoic acid hydrochlorides under alkaline conditions to give four stereoisomers of CYT.

L-CYSTATHIONINE DERIVATIVES FOR THE SYNTHESIS OF PEPTIDES

The preparation is described of L-cystathionine derivatives with amino protecting groups, which can readily be cleaved acidolytically and permit a selective acylation of both amino groups, and of a derivative with carboxyls protected by different groups.