N’-Formylkynurenine

• CAT Number: R043934
• CAS Number: 1022-31-7
• Molecular Formula: C11H12N2O4
• Molecular Weight: 236.227
• Purity: ≥95%
• Storage: 4°C
• IUPAC Name: 2-amino-4-(2-formamidophenyl)-4-oxobutanoic acid
• InChI: InChI=1S/C11H12N2O4/c12-8(11(16)17)5-10(15)7-3-1-2-4-9(7)13-6-14/h1-4,6,8H,5,12H2,(H,13,14)(H,16,17)
• InChIKey: BYHJHXPTQMMKCA-UHFFFAOYSA-N
• SMILES: C1=CC=C(C(=C1)C(=O)CC(C(=O)O)N)NC=O

N-formylkynurenine(CAS: 1022-31-7） is a non-proteinogenic alpha-amino acid and a non-proteinogenic amino acid derivative. It derives from a kynurenine.

Reference

[1]. Int J Radiat Biol Relat Stud Phys Chem Med. 1976 Aug;30(2):189-92. doi: 10.1080/09553007614550941.
N'-formylkynurenine-photosensitized inactivation of bacteriophage.
Walrant P, Santus R, Redpath JL, Pileni MP.
DOI: 10.1080/09553007614550941 PMID: 1086300 [Indexed for MEDLINE]

[2]. J Biol Chem. 2011 Jun 24;286(25):22632-41. doi: 10.1074/jbc.M110.212928. Epub 2011 Apr 28.
N-formylkynurenine as a marker of high light stress in photosynthesis.
Dreaden TM(1), Chen J, Rexroth S, Barry BA.
Author information: (1)School of Chemistry and Biochemistry and Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.
Photosystem II (PSII) is the membrane protein complex that catalyzes the photo-induced oxidation of water at a manganese-calcium active site. Light-dependent damage and repair occur in PSII under conditions of high light stress. The core reaction center complex is composed of the D1, D2, CP43, and CP47 intrinsic polypeptides. In this study, a new chromophore formed from the oxidative post-translational modification of tryptophan is identified in the CP43 subunit. Tandem mass spectrometry peptide sequencing is consistent with the oxidation of the CP43 tryptophan side chain, Trp-365, to produce N-formylkynurenine (NFK). Characterization with ultraviolet visible absorption and ultraviolet resonance Raman spectroscopy supports this assignment. An optical assay suggests that the yield of NFK increases 2-fold (2.2 ± 0.5) under high light illumination. A concomitant 2.4 ± 0.5-fold decrease is observed in the steady-state rate of oxygen evolution under the high light conditions. NFK is the product formed from reaction of tryptophan with singlet oxygen, which can be produced under high light stress in PSII. Reactive oxygen species reactions lead to oxidative damage of the reaction center, D1 protein turnover, and inhibition of electron transfer. Our results are consistent with a role for the CP43 NFK modification in photoinhibition.
DOI: 10.1074/jbc.M110.212928 PMCID: PMC3121407 PMID: 21527632 [Indexed for MEDLINE]

[3]. Anal Bioanal Chem. 2013 Mar;405(8):2515-24. doi: 10.1007/s00216-012-6650-y. Epub 2013 Jan 12.
Formation of an N-formylkynurenine-derived fluorophore and its use for measuring indoleamine 2,3-dioxygenase 1 activity.
Tomek P(1), Palmer BD, Flanagan JU, Fung SP, Bridewell DJ, Jamie JF, Ching LM.
Author information: (1)Auckland Cancer Society Research Centre and Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland, New Zealand.
Indoleamine 2,3-dioxygenase 1 (IDO1) is a tryptophan-catabolizing enzyme whose expression by a broad range of clinical tumors is associated with immunosuppression and poor patient outcome. Here we describe a new fluorescence assay for measuring IDO1 activity suitable for high-throughput screening of compound libraries for novel IDO1 inhibitors. This assay is easy to perform, requiring the addition of only one reagent prior to readout. In place of measuring kynurenine, it uses the in situ formation of an N-formylkynurenine-derived fluorophore (NFKPIP) measured at an excitation wavelength of 400 nm and an emission wavelength of 500 nm. The fluorescence intensity of the NFKPIP formed is directly related to the amount of enzyme activity, and the signal is stable over 8 h. This assay has a lower limit of detection, equating to 153 nM N-formylkynurenine, which is over 30-fold lower than the limits of detection of existing assays for IDO1 activity. When we compared the performance of the new assay with that of the published colorimetric absorbance assay in screening the National Cancer Institute Diversity Set III of 1,597 compounds for IDO1 inhibitors, we obtained an identical list of the 25 most active compounds in the two assays. Although 93 compounds (aldehydes, ketones, and aromatic amines) in the library interfered with the absorbance readout, only 18 compounds (conjugated systems and fused cycles) interfered with the readout of the new fluorescence assay. IC(50) values determined using the new assay for three known IDO1 inhibitors-1,4-naphthoquinone, 4-amino-N-(3-chloro-4-fluorophenyl)-N'-hydroxy-1,2,5-oxadiazole-3-carboximidamide and 4-phenyl-1H-imidazole-were consistent with their literature values, further validating the new assay for measuring IDO1 activity.
DOI: 10.1007/s00216-012-6650-y PMID: 23314482 [Indexed for MEDLINE]

[4]. J Am Chem Soc. 2011 Oct 12;133(40):16251-7. doi: 10.1021/ja207066z. Epub 2011 Sep 19.
The mechanism of formation of N-formylkynurenine by heme dioxygenases.
Basran J(1), Efimov I, Chauhan N, Thackray SJ, Krupa JL, Eaton G, Griffith GA, Mowat CG, Handa S, Raven EL.
Author information: (1)Department of Biochemistry, University of Leicester, Lancaster Road, Leicester LE1 9HN, United Kingdom.
Heme dioxygenases catalyze the oxidation of L-tryptophan to N-formylkynurenine (NFK), the first and rate-limiting step in tryptophan catabolism. Although recent progress has been made on early stages in the mechanism, there is currently no experimental data on the mechanism of product (NFK) formation. In this work, we have used mass spectrometry to examine product formation in a number of dioxygenases. In addition to NFK formation (m/z = 237), the data identify a species (m/z = 221) that is consistent with insertion of a single atom of oxygen into the substrate during O(2)-driven turnover. The fragmentation pattern for this m/z = 221 species is consistent with a cyclic amino acetal structure; independent chemical synthesis of the 3a-hydroxypyrroloindole-2-carboxylic acid compound is in agreement with this assignment. Labeling experiments with (18)O(2) confirm the origin of the oxygen atom as arising from O(2)-dependent turnover. These data suggest that the dioxygenases use a ring-opening mechanism during NFK formation, rather than Criegee or dioxetane mechanisms as previously proposed.
DOI: 10.1021/ja207066z PMCID: PMC3210546 PMID: 21892828 [Indexed for MEDLINE]

[5]. Photochem Photobiol. 1975 Jul-Aug;22(1-2):63-5. doi: 10.1111/j.1751-1097.1975.tb06723.x.
Photosensitizing properties of N-formylkynurenine.
Walrant P, Santus R, Grossweiner LI.
DOI: 10.1111/j.1751-1097.1975.tb06723.x PMID: 1187809 [Indexed for MEDLINE]