621-44-3Relevant articles and documents
Scavengers for peroxynitrite: Inhibition of tyrosine nitration and oxidation with tryptamine derivatives, α-lipoic acid and synthetic compounds
Nakagawa, Hidehiko,Sumiki, Erika,Takusagawa, Mitsuko,Ikota, Nobuo,Matsushima, Yoshikazu,Ozawa, Toshihiko
, p. 261 - 265 (2000)
The inhibitory effects of various endogenous and synthetic compounds on the nitration and oxidation of L-tyrosine by peroxynitrite were examined. Nitrating and oxidizing activities were monitored by the formation of 3- nitrotyrosine and dityrosine with a HPLC-UV-fluorescence detector system, respectively. Glutathione, serotonin and synthetic sulfur- and selenium- containing compounds inhibited both the nitration and oxidation reaction of L-tyrosine effectively. However, 5-methoxytryptamine, melatonin and α-lipoic acid only inhibited the nitration reaction, and enhanced the formation of an oxidation product. This is important evidence that there are different intermediates in the nitrating and oxidizing reactions of L-tyrosine by peroxynitrite. It was suggested that 5-methoxytryptamine, melatonin and α- lipoic acid reacted only with the nitrating intermediate of peroxynitrite and inhibited nitration of L-tyrosine. Actually, the DNA strand breakage, which is believed to be a typical reaction of hydroxyl radical-like species, caused by peroxynitrite was not effectively inhibited by 5-methoxytryptamine. 5- Methoxytryptamine, melatonin and α-lipoic acid were viewed as useful reagents for investigating the mechanisms of damage by peroxynitrite in vitro.
Selective scavenging property of the indole moiety for the nitrating species of peroxynitrite
Nakagawa, Hidehiko,Takusagawa, Mitsuko,Arima, Hiromi,Furukawa, Kumiko,Kinoshita, Takeshi,Ozawa, Toshihiko,Ikota, Nobuo
, p. 146 - 149 (2004)
The inhibitory effect on tyrosine nitration and oxidation of peroxynitrite was evaluated for more than 40 reagents including natural and synthetic compounds, and the inhibiting efficiency of each compound for nitration was compared with that for oxidation, to characterize its property as a peroxynitrite scavenger. In the presence of various concentrations of testing compounds, the nitrating and oxidizing activities were measured by monitoring the formation of 3-nitrotyrosine and dityrosine with an HPLC-UV-fluorescence detector. The IC50 values for nitration and oxidation were determined, and the ratio of these two IC50 values was calculated for each compound. Although the IC50 values varied from compound to compound, it was revealed that the ratio of two IC50 values (IC 50 for oxidation/IC50 for nitration) was 1 in almost all the compounds tested, except five indole derivatives (L-tryptophan, melatonin, 5-methoxytryptamine, tryptamine, and tetrahydro-beta-carboline) and one synthetic selenium-containing compound ((2R,3R,4S)-2-amino-3,4-dihydroxy-5- phenylselenopentan-1-ol, ADPP). The indole derivatives showed a specific inhibitory effect on tyrosine nitration without affecting the oxidation. ADPP was confirmed to have a preferable inhibitory activity for tyrosine oxidation. It was suggested that compounds showing an IC50 value ratio of 1 scavenged the common species for nitration and oxidation, while the indole derivatives and ADPP preferably scavenged the nitrating and oxidizing species, respectively. From a stopped flow study, it was also revealed that the nitrotyrosine formation was relatively slow, unlike an OH radical reaction. These results imply that the peroxynirite reaction at least partly proceeds through specific species for nitration.
Inhibition of nitrous acid-dependent tyrosine nitration and DNA base deamination by flavonoids and other phenolic compounds
Oldreive, Ceri,Zhao, Kaicun,Paganga, George,Halliwell, Barry,Rice-Evans, Catherine
, p. 1574 - 1579 (1998)
Exposure of tyrosine or DNA bases to acidic nitrite at low pH results in the nitration of tyrosine and the formation of base deamination products, respectively. At pH 1, hypoxanthine and xanthine are formed from the deamination of adenine and guanine, respectively, whereas under the same conditions, uracil is not detected. The yield of 3-nitrotyrosine derived from interaction of equimolar nitrite and tyrosine at pHI is approximately 50% of that obtained from equimolar peroxynitrite-tyrosine interactions at pH 7.4. The ability of a range of plant phenolic constituents to prevent damage mediated by acidic nitrite was also examined in comparison with the activity of vitamin C. The epicatechin/gallate family of flavonols, constituents of green tea, red wine, etc., demonstrates the most extensive inhibitory properties against both tyrosine nitration and base deamination. The results also show that ascorbic acid is a poor inhibitor of nitration or deamination under acidic conditions such as those of the stomach. The ability of plant phenolics to scavenge reactive nitrogen species derived from acidic nitrite may contribute to the protective effects of tea polyphenols against gastric cancer.
A novel procedure for generating both nitric oxide and superoxide in situ from chemical sources at any chosen mole ratio. First application: Tyrosine oxidation and a comparison with preformed peroxynitrite
Hodges, George R.,Marwaha, Jasvir,Paul, Thomas,Ingold
, p. 1287 - 1293 (2000)
The first method for generating ·NO and O2·- at any known, constant ratio has been developed. Spermine NONOate and di(4-carboxybenzyl)hyponitrite decay with first-order kinetics and exactly equal rate constants (half-lives of 80 min) at 37 °C and pH 7.5 to give 200 and 40 mol % ·NO and O2·- respectively. Tyrosine oxidation to dityrosine and 3-nitrotyrosine (the major and minor products under the conditions used in these experiments) has been studied (mainly in the presence of CO2) using various different ratios of the rates of formation of ·NO and O2·-. The ·NO/O2·- = 1.0 product profiles are very similar to those of the products derived from equal amounts of ·NO and O2·- generated at a ·NO/O2·- ratio of 1.0 from SIN-1 but are very different from those derived from preformed peroxynitrite. All the experimental results can be explained in terms of free radical chemistry. The product profiles at all the ·NO/O2·- ratios could be satisfactorily simulated provided an important group of reactions which lead to the consumption of dityrosine was included.
pH-Dependent Nitrotyrosine Formation in Ribonuclease A is Enhanced in the Presence of Polyethylene Glycol (PEG)
Roy, Pritam,Panda, Atashi,Hati, Sumon,Dasgupta, Swagata
, p. 4780 - 4792 (2019)
Protein nitration can occur as a result of peroxynitrite-mediated oxidative stress. Excess production of peroxynitrite (PN) within the cellular medium can cause oxidative damage to biomolecules. The in vitro nitration of Ribonuclease A (RNase A) results in nitrotyrosine (NT) formation with a strong dependence on the pH of the medium. In order to mimic the cellular environment in this study, PN-mediated RNase A nitration has been carried out in a crowded medium. The degree of nitration is higher at pH 7.4 (physiological pH) compared to pH 6.0 (tumor cell pH). The extent of nitration increases significantly when PN is added to RNase A in the presence of crowding agents PEG 400 and PEG 6000. PEG has been found to stabilize PN over a prolonged period, thereby increasing the degree of nitration. NT formation in RNase A also results in a significant loss in enzymatic activity.
15N CIDNP investigations of the peroxynitric acid nitration of l-tyrosine and of related compounds
Lehnig, Manfred,Kirsch, Michael
, p. 721 - 729 (2006)
Peroxynitric acid (O2NOOH) nitrates l-tyrosine and related compounds at pH 2-5. During reaction with O215NOOH in the probe of a 15N NMR spectrometer, the NMR signals of the nitration products of l-tyrosine, N-acetyl-l-tyrosine, 4-fluorophenol and 4-methoxyphenylacetic acid appear in emission indicating a nitration via free radicals. Nuclear polarizations are built up in radical pairs [ 15NO2, PhO]F or [15NO2, ArH+]F formed by diffusive encounters of 15NO2 with phenoxyl-type radicals PhO or with aromatic radical cations ArH+. Quantitative 15N CIDNP investigations with N-acetyl-l-tyrosine and 4-fluorophenol show that the radical-dependent nitration is the only reaction pathway. During the nitration reaction, the 15N NMR signal of 15NO3 - also appears in emission. This is explained by singlet-triplet transitions in radical pairs [15NO2, 15NO 3]S generated by electron transfer between O 215NOOH and H15NO2 formed as a reaction intermediate. During reaction of peroxynitric acid with ascorbic acid, 15N CIDNP is again observed in the 15N NMR signal of 15NO3- showing that ascorbic acid is oxidized by free radicals. In contrast to this, O215NOOH reacts with glutathione and cysteine without the appearance of 15N CIDNP, indicating a direct oxidation without participation of free radicals. The Royal Society of Chemistry.
Functional hybrids of layered double hydroxides with hemin: Synergistic effect for peroxynitrite-scavenging activity
Qiao, Fengmin,Shi, Weijie,Dong, Jing,Lv, Wei,Ai, Shiyun
, p. 44614 - 44620 (2014)
Hemin has been successfully modified onto the surface of CuAl layered double hydroxide nanosheets by a simple coprecipitation process, which afforded a hemin modified CuAl layered double hydroxide (H-LDH) hybrid functional material that exhibited protective effects against the harmful ONOO-. The obtained products were characterized by X-ray powder diffraction, scanning electron microscopy, transmission electron microscopy and Fourier transform infrared spectroscopy, which showed that the samples had hexagonal symmetry structure with a mean lateral size of 1 μm, on the surface of which were adsorbed round particles with a diameter of about 300 nm. A detailed inhibition study on ONOO--mediated nitration reactions indicated that the interaction between hemin and LDHs results in a synergistic effect, which leads to an efficient reduction of ONOO- to nitrate. The present study suggests that the H-LDHs had an efficient ONOO- scavenging ability, and may well be a potent ONOO- scavenger for protection of the cellular defense activity against ONOO- involved diseases.
Photosensitized production of nitric oxide and peroxynitrite from a carbon-bound diazenium diolate and 2-methyl-2-nitrosopropane
Sanchez-Cruz, Pedro,Alegria, Antonio E.
, p. 79 - 85 (2016)
The photosensitized generation of nitric oxide from alanosine (3-(hydroxynitrosoamino)-D,L-alanine) by aluminum phthalocyanine tetrasulfonate (AlPcS4) is reported. While nitric oxide (NO) is obtained in nitrogen-saturated solutions, evidence suggest that both NO and peroxynitrite are produced in air-saturated solutions. Enhancement of NO production occurs in the presence of ubiquinone-0. These observations support the idea that NO is produced by the photosensitized oxidation of alanosine. Both NO and peroxynitrite are detected during photoirradiation of AlPcS4 in the presence of 2-methyl-2-nitrosopropane (MNP) and hypoxanthine (HX), but not in the absence of HX, in air-saturated solutions, thus implying that HX is acting as sacrificial electron donor, thus promoting superoxide formation.
Tyrosine nitration in peptides by peroxynitrite generated in situ in a light-controlled platform: Effects of pH and thiols
Deboer, Tara R.,Palomino, Rafael I.,Idiga, Sharon O.,Millhauser, Glenn L.,Mascharak, Pradip K.
, p. 24 - 30 (2014)
Peroxynitrite has been shown to play a critical role in inflammation and affords 3-nitrotyrosine as the hallmark product. The reported methods of generating this reactive nitrogen species in situ often fails to provide a high and steady flux of peroxynitrite resulting in poor yields of 3-nitrotyrosine. Herein we report a two-component peroxynitrite-generating platform in which this anion is produced in a biomimetic fashion and under the control of visible light. Incorporation of the nitric oxide- and superoxide-generating components in polymer matrices allows easy alterations of pH in the reaction wells of this platform. We have demonstrated very efficient nitration of tyrosine by peroxynitrite at different pH values and with varying concentrations of carbonate. In addition to tyrosine, a set of tyrosine-containing peptides was also studied. Presence of glutathione in the reaction wells increases the extent of tyrosine nitration in such peptide substrates presumably by raising the lifetime of nitric oxide in the reaction medium. When a cysteine residue was included in the sequence of the peptide, the extent of nitration of the tyrosine residue was found to depend on the position of the cysteine residue with respect to tyrosine. The extent of tyrosine nitration is strongly attenuated when the cysteine residue is directly adjacent to the tyrosine. This effect has been attributed to an intramolecular radical transfer mechanism. Taken together, results of this study demonstrate the potential of this light-controlled platform as a convenient bioanalytical tool in studying the reactions of peroxynitrite under widely varying conditions.
Identification and characterization of a bacterial cytochrome P450 monooxygenase catalyzing the 3-nitration of tyrosine in rufomycin biosynthesis
Tomita, Hiroya,Katsuyama, Yohei,Minami, Hiromichi,Ohnishi, Yasuo
, p. 15859 - 15869 (2017)
Rufomycin is a circular heptapeptide with anti-mycobacterial activity and is produced by Streptomyces atratus ATCC 14046. Its structure contains three non-proteinogenic amino acids, N-dimethylallyltryptophan, trans-2-crotylglycine, and 3-nitro-tyrosine (3NTyr). Although the rufomycin structure was already reported in the 1960s, its biosynthesis, including 3NTyr generation, remains unclear. To elucidate the rufomycin biosynthetic pathway, we assembled a draft genome sequence of S. atratus and identified the rufomycin biosynthetic gene cluster (ruf cluster), consisting of 20 ORFs (rufA–rufT). We found a putative heptamodular nonribosomal peptide synthetase encoded by rufT, a putative tryptophan N-dimethylallyltransferase encoded by rufP, and a putative trimodular type I polyketide synthase encoded by rufEF. Moreover, the ruf cluster contains an apparent operon harboring putative cytochrome P450 (rufO) and nitric oxide synthase (rufN) genes. A similar operon, txtDE, is responsible for the formation of 4-nitrotryptophan in thaxtomin biosynthesis; the cytochrome P450 TxtE catalyzes the 4-nitration of Trp. Therefore, we hypothesized that RufO should catalyze the Tyr 3-nitration. Disruption of rufO abolished rufomycin production by S. atratus, which was restored when 3NTyr was added to the culture medium of the dis-ruptant. Recombinant RufO protein exhibited Tyr 3-nitra-tion activity both in vitro and in vivo. Spectroscopic analysis further revealed that RufO recognizes Tyr as the substrate with a dissociation constant of 0.1 M. These results indicate that RufO is an unprecedented cytochrome P450 that catalyzes Tyr nitration. Taken together with the results of an in silico analysis of the ruf cluster, we propose a rufomycin biosynthetic pathway in S. atratus.
