2922-83-0

Basic information

• Product Name: L-KYNURENINE
• Synonyms: L-2-AMINO-3-(2-AMINOBENZOYL)PROPIONIC ACID;L-2-AMINO-4-[2-AMINOPHENYL]-4-OXOBUTANOIC ACID;L-KYNURENINE;L-kynurenine free base;β-Anthraniloyl-L-alanine;β-Anthraniloyl-L-alanine, L-2-Amino-4-(2-aminophenyl)-4-oxobutanoic acid;L-Kynurenine Hydrate;(S)-2-Amino-4-oxo-4-(2-aminophenyl)butanoic acid
• CAS NO: 2922-83-0
• Molecular Formula: C₁₀H₁₂N₂O₃
• Molecular Weight: 208.21
• Product Categories: Amino Acids;Biochemistry;non-Proteinorganic Amino Acids;Amino Acids
• Mol File: 2922-83-0.mol

Chemical Properties

• Melting Point: 219℃ (decomposition) (ethanol )
• Boiling Point: 466.6 °C at 760 mmHg
• Flash Point: 236 °C
• Appearance: light yellow/crystalline
• Density: 1.343 g/cm³
• Refractive Index: -33 ° (C=0.4, H2O)
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• Solubility: Soluble in DMSO (up to 2 mg/ml) or in Water (up to 2 mg/ml).
• PKA: 2.21±0.23(Predicted)
• Stability: Stable for 2 years as supplied. Solutions in DMSO or distilled water may be stored at -20° for up to 3 months.
• Merck: 14,5328
• CAS DataBase Reference: L-KYNURENINE(CAS DataBase Reference)
• NIST Chemistry Reference: L-KYNURENINE(2922-83-0)
• EPA Substance Registry System: L-KYNURENINE(2922-83-0)

Safety Data

• WGK Germany: 3
• RTECS: CY9049700
• Hazardous Substances Data: 2922-83-0(Hazardous Substances Data)

Usage

Uses

Used in Research and Diagnostics:
L-Kynurenine is used as a standard for indoleamine-2,3-dioxygenase (IDO) assay, which is an essential enzyme involved in the catabolism of tryptophan and the production of L-kynurenine. This application aids in understanding the role of IDO in various biological processes and its potential as a therapeutic target.
Used in Biochemical Analysis:
L-Kynurenine serves as a standard to extract and quantify kynurenine from cultured cells and media. This application is crucial for studying the metabolic pathways of tryptophan and the role of kynurenine in cellular processes, particularly in the context of cancer biology.
Used in Pharmaceutical Industry:
L-Kynurenine can be used as a starting material or intermediate in the synthesis of various pharmaceutical compounds, particularly those targeting the kynurenine pathway and its associated enzymes. This application can lead to the development of novel therapeutics for conditions related to tryptophan metabolism and immune regulation.
Used in Nutritional Supplements:
L-Kynurenine may be utilized in the development of nutritional supplements aimed at supporting immune function and overall health. By modulating the kynurenine pathway, these supplements could potentially help maintain a balanced immune response and promote general well-being.

Biochem/physiol Actions

Key intermediate in the breakdown pathway of tryptophan.

References

References/Citations 1) Ibana?et al. (2011),?Inhibition of indoleamine 2,3-dioxygenase activity by levo-1-methyl tryptophan blocks gamma interferon-induced Chlaydia trachomatis persistence in human epithelial cells; Infect. Immun.,?79?4425 2) Opitz?et al. (2011),?An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor; Nature,?478?197

InChI:InChI=1/C10H12N2O3/c11-7-4-2-1-3-6(7)9(13)5-8(12)10(14)15/h1-4,8H,5,11-12H2,(H,14,15)/t8-/m0/s1

Upstream product

• 73-22-3 L-Tryptophan 
• 32999-55-6 oxindolylalanine 
• 32999-55-6 2-Amino-3-(2-oxo-2,3-dihydro-1H-indol-3-yl)-propionic acid 
• 117269-81-5 L-Kynurenine dihydrobromide 
• 615-43-0 2-iodophenylamine 
• 343-65-7 Kynurenine 
• 236094-74-9 2-amino-3-(2-oxoindolin-3-yl)propanoic acid 
• 3978-11-8 (S )-2-Amino-4-(2-formamidophenyl)-4-oxobutanoic acid 
• 172479-59-3 (2S)-Methyl 2-(N-tert-butoxycarbonylamino)-4-oxo-4-(2'-aminophenyl)butanoate 
• 73-22-3 L-tryptophan 

Downstream Products

• 56-41-7 L-alanin 
• 13948-23-7 2-amino-4-(2-amino-phenyl)-4-hydroxy-butyric acid 
• 74802-08-7 N^α-t-butyloxycarbonyl-L-kynurenine 
• 363-36-0 kynuramine 
• 135457-24-8 (4R)-dihydro-L-kynurenine 
• 135457-25-9 (4S)-dihydro-L-kynurenine 
• 135457-26-0 (2S,4R)-2-amino-4-hydroxy-4-phenylbutanoic acid 
• 146297-34-9 (2S,4S)-2-amino-4-hydroxy-4-phenylbutanoic acid 
• 160724-38-9 2-carboxy-5,6-dihydro-4H-pyrido<2,3,4-kl>acridine 
• 118-92-3 anthranilic acid 

Relevant articles and documents

Structures of bacterial kynurenine formamidase reveal a crowded binuclear zinc catalytic site primed to generate a potent nucleophile

Tryptophan is an important precursor for chemical entities that ultimately support the biosynthesis of key metabolites. The second stage of tryptophan catabolism is catalysed by kynurenine formamidase, an enzyme that is different between eukaryotes and prokaryotes. In the present study, we characterize the catalytic properties and present the crystal structures of three bacterial kynurenine formamidases. The structures reveal a new amidase protein fold, a highly organized and distinctive binuclear Zn2+ catalytic centre in a confined, hydrophobic and relatively rigid active site. The structure of a complex with 2-aminoacetophenone delineates aspects of molecular recognition extending to the observation that the substrate itself may be conformationally restricted to assist binding in the confined space of the active site and for subsequent processing. The cations occupy a crowded environment, and, unlike most Zn2+ -dependent enzymes, there is little scope to increase co-ordination number during catalysis.We propose that the presence of a bridging water/hydroxide ligand in conjunction with the placement of an active site histidine supports a distinctive amidation mechanism.

A novel photocatalytic conversion of tryptophan to kynurenine using black light as a light source

The photocatalytic conversion of an aqueous solution of l-tryptophan (Trp) to kynurenine (KN) was investigated under the illumination of different light sources. Results show that Trp converted to KN with a selectivity of 64% under the illumination of a medium pressure (MP) Hg lamp. KN selectivity was increased to >90% when black light (BL) was used a light source. The novel use of BL in the photocatalytic conversion of Trp to KN significantly reduces the energy consumption compared with MP light.

In vitro modulation of cytochrome p450 reductase supported indoleamine 2,3-dioxygenase activity by allosteric effectors cytochrome b5 and methylene blue

Indoleamine 2,3-dioxygenase (IDO) is a heme-containing dioxygenase involved in the degradation of several indoleamine derivatives and has been indicated as an immunosuppressive. IDO is an attractive target for therapeutic intervention in diseases which are known to capitalize on immune suppression, including cancer, HIV, and inflammatory diseases. Conventionally, IDO activity is measured through chemical reduction by the addition of ascorbate and methylene blue. Identification of potential coenzymes involved in the reduction of IDO in vivo should improve in vitro reconstitution systems used to identify potential IDO inhibitors. In this study we show that NADPH-cytochrome P450 reductase (CPR) is capable of supporting IDO activity in vitro and that oxidation of L-Trp follows substrate inhibition kinetics (kcat = 0.89 ± 0.04 s -1 , Km = 0.72 ±0.15 μM, and Ki = 9.4 ± 2.0 μM). Addition of cytochrome b5 to CPR-supported L-Trp incubations results in modulation from substrate inhibition to sigmoidal kinetics (kcat = 1.7 ± 0.3 s-1, Km = 1.5 ± 0.9 μM, and Ki = 1.9 ± 0.3). CPR-supported D-Trp oxidations (±cytochrome b5) exhibit Michaelis-Menten kinetics. Addition of methylene blue (minus ascorbate) to CPR-supported reactions resulted in inhibition of DTrp turnover and modulation of L-Trp kinetics from allosteric to Michaelis-Menten with a concurrent decrease in substrate affinity for IDO. Our data indicate that CPR is capable of supporting IDO activity in vitro and oxidation of tryptophan by IDO displays substrate stereochemistry dependent atypical kinetics which can be modulated by the addition of cytochrome b5.

Spectroscopic studies of ligand and substrate binding to human indoleamine 2,3-dioxygenase

Human indoleamine 2,3-dioxygenase (hIDO) is an intracellular heme-containing enzyme, which catalyzes the initial and rate-determining step of l-tryptophan (l-Trp) metabolism via the kynurenine pathway in nonhepatic tissues. Steady-state kinetic data showed that hIDO exhibits substrate inhibition behavior, implying the existence of a second substrate binding site in the enzyme, although so far there is no direct evidence supporting it. The kinetic data also revealed that the Km of l-Trp (15 μM) is ～27-fold lower than the Kd of l-Trp (0.4 mM) for the ligand-free ferrous enzyme, suggesting that O2 binding proceeds l-Trp binding during the catalytic cycle. With cyanide as a structural probe, we have investigated the thermodynamic and kinetic parameters associated with ligand and substrate binding to hIDO. Equilibrium titration studies show that the cyanide adduct is capable of binding two l-Trp molecules, with Kd values of 18 μM and 26 mM. The data offer the first direct evidence of the second substrate binding site in hIDO. Kinetic studies demonstrate that prebinding of l-Trp to the enzyme retards cyanide binding by ～13-fold, while prebinding of cyanide to the enzyme facilitates l-Trp binding by ～22-fold. The data support the view that during the active turnover of the enzyme it is kinetically more favored to bind O2 prior to l-Trp.

Evaluation of the Edman degradation product of vancomycin bonded to core-shell particles as a new HPLC chiral stationary phase

A modified macrocyclic glycopeptide-based chiral stationary phase (CSP), prepared via Edman degradation of vancomycin, was evaluated as a chiral selector for the first time. Its applicability was compared with other macrocyclic glycopeptide-based CSPs: TeicoShell and VancoShell. In addition, another modified macrocyclic glycopeptide-based CSP, NicoShell, was further examined. Initial evaluation was focused on the complementary behavior with these glycopeptides. A screening procedure was used based on previous work for the enantiomeric separation of 50 chiral compounds including amino acids, pesticides, stimulants, and a variety of pharmaceuticals. Fast and efficient chiral separations resulted by using superficially porous (core-shell) particle supports. Overall, the vancomycin Edman degradation product (EDP) resembled TeicoShell with high enantioselectivity for acidic compounds in the polar ionic mode. The simultaneous enantiomeric separation of 5 racemic profens using liquid chromatography-mass spectrometry with EDP was performed in approximately 3?minutes. Other highlights include simultaneous liquid chromatography separations of rac-amphetamine and rac-methamphetamine with VancoShell, rac-pseudoephedrine and rac-ephedrine with NicoShell, and rac-dichlorprop and rac-haloxyfop with TeicoShell.

N 1-fluoroalkyltryptophan analogues: Synthesis and in vitro study as potential substrates for indoleamine 2,3-dioxygenase

Indoleamine 2,3-dioxygenase (hIDO) is an enzyme that catalyzes the oxidative cleavage of the indole ring of l-tryptophan through the kynurenine pathway, thereby exerting immunosuppressive properties in inflammatory and tumoral tissues. The syntheses of 1-(2-fluoroethyl)-tryptophan (1-FETrp) and 1-((1-(2-fluoroethyl)-1H-1,2,3-triazol-4-yl)methyl)-tryptophan, two N1-fluoroalkylated tryptophan derivatives, are described here. In vitro enzymatic assays with these two new potential substrates of hIDO show that 1-FETrp is a good and specific substrate of hIDO. Therefore, its radioactive isotopomer, 1-[18F]FETrp, should be a molecule of choice to visualize tumoral and inflammatory tissues and/or to validate new potential inhibitors.

Synthesis of peptides containing 5-hydroxytryptophan, oxindolylalanine, N-formylkynurenine and kynurenine

ROS, continuously produced in cells, can reversibly or irreversibly oxidize proteins, lipids, and DNA. At the protein level, cysteine, methionine, tryptophan, and tyrosine residues are particularly prone to oxidation. Here, we describe the solid phase synthesis of peptides containing four different oxidation products of tryptophan residues that can be formed by oxidation in proteins in vitro and in vivo: 5-HTP, Oia, Kyn, and NFK. First, we synthesized Oia and NFK by selective oxidation of tryptophan and then protected the ${bf alpha}$-amino group of both amino acids, and the commercially available 5-HTP, with Fmoc-succinimide. High yields of Fmoc-Kyn were obtained by acid hydrolysis of Fmoc-NFK. All four Fmoc derivatives were successfully incorporated, at high yields, into three different peptide sequences from skeletal muscle actin, creatin kinase (M-type), and ${bf beta}$-enolase. The correct structure of all modified peptides was confirmed by tandem mass spectrometry. Interestingly, isobaric peptides containing 5-HTP and Oia were always well separated in an acetonitrile gradient with TFA as the ion-pair reagent on a C18-phase. Such synthetic peptides should prove useful in future studies to distinguish isobaric oxidation products of tryptophan.

COMPOSITIONS AND METHODS FOR CYCLOFRUCTANS AS SEPARATION AGENTS

The present invention relates to derivatized cyclofructan compounds, compositions comprising derivatized cyclofructan compounds, and methods of using compositions comprising derivatized cyclofructan compounds for chromatographic separations of chemical species, including enantiomers. Said compositions may comprise a solid support and/or polymers comprising derivatized cyclofructan compounds.

Plant phenolics affect oxidation of tryptophan

The effect of berry phenolics such as anthocyanins, ellagitannins, and proanthocyanidins from raspberry (Rubus idaeus), black currant (Ribes nigrum), and cranberry (Vaccinium oxycoccus) and byproducts of deoiling processes rich in phenolics such as rapese

Enantioselective synthesis of aroylalanine derivatives

In this paper we report the development of a highly enantioselective method for the synthesis of aroylalanines. The approach described employs a protected 2-amino-4-bromopent-4-enoic acid, generated via the asymmetric phase-transfer catalyzed alkylation of a glycine imine, as a key intermediate. Suzuki coupling with an aryl boronic acid followed by ozonolysis of the resulting styrene provides efficient access to the aroylalanine derivatives. The utility of this methodology is illustrated by the synthesis of L-kynurenine along with several aroylalanine inhibitors of the kynurenine pathway.