63442-81-9

Basic information

• Product Name: o,o′-dityrosine
• Synonyms: o,o′-dityrosine
• CAS NO: 63442-81-9
• Molecular Weight: 360.367
• Mol File: 63442-81-9.mol

Chemical Properties

• CAS DataBase Reference: o,o′-dityrosine(CAS DataBase Reference)
• NIST Chemistry Reference: o,o′-dityrosine(63442-81-9)
• EPA Substance Registry System: o,o′-dityrosine(63442-81-9)

Safety Data

• Hazardous Substances Data: 63442-81-9(Hazardous Substances Data)

Upstream product

• 16978-66-8 L-tyrosine radical 
• 60-18-4 L-tyrosine 
• 556-02-5 tyrosine 

Relevant articles and documents

Formation and characterization of crosslinks, including Tyr-Trp species, on one electron oxidation of free Tyr and Trp residues by carbonate radical anion

Dityrosine and ditryptophan bonds have been implied in protein crosslinking. This is associated with oxidative stress conditions including those involved in neurodegenerative pathologies and age-related processes. Formation of dityrosine and ditryptophan derives from radical-radical reactions involving Tyr and Trp radicals. However, cross reactions of Tyr and Trp leading to Tyr-Trp crosslinks and their biological consequences have been less explored. In the present work we hypothesized that exposure of free Tyr and Trp to a high concentration of carbonate anion radicals (CO3-), under anaerobic conditions, would result in the formation of Tyr-Trp species, as well as dityrosine and ditryptophan crosslinks. Here we report a simple experimental procedure, employing CO3- generated photochemically by illumination of a Co(iii) complex at 254 nm, that produces micromolar concentrations of Tyr-Trp crosslinks. Analysis by mass spectrometry of solutions containing only the individual amino acids, and the Co(iii) complex, provided evidence for the formation of o,o′-dityrosine and isodityrosine from Tyr, and three ditryptophan dimers from Trp. When mixtures of Tyr and Trp were illuminated in an identical manner, Tyr-Trp crosslinks were detected together with dityrosine and ditryptophan dimers. These results indicate that there is a balance between the formation of these three classes of crosslinks, which is dependent on the Tyr and Trp concentrations. The methods reported here allow the generation of significant yields of isolated Tyr-Trp adducts and their characterization. This technology should facilitate the detection, and examination of the biological consequences of Tyr-Trp crosslink formation in complex systems in future investigations.

Synthesis, Ligand Binding and Biomimetic Oxidations of Deuterohaemin modified with an Undecapeptide Residue

Deuterohaemin has been covalently linked to the undecapeptide Ala-Phe-Ser-Phe-Glu-Ala-Gln-Gly-Gly-Leu-Ala at one of the propionic acid side chains.The binding equilibria between the resulting deuterohaemin-undecapeptide complex and imidazole occur in two steps; the first molecule of the ligand binds with high affinity (K1 = 1500 dm3 mol-1), while for the second molecule the affinity is markedly lower (K2 = 220 dm3 mol-1), indicating that folding of the peptide chain in the monoimidazole adduct severely limits the accessibility of the sixth iron co-ordination position.The complex exhibits both catalase and peroxidase activity towards reducing substrates in the presence of hydrogen peroxide.In catalytic sulphoxidations of a series of para-substituted thioanisoles, p-XC6H4SMe, by hydrogen peroxide a good correlation has been found between the relative rates and the Hammett ?p values, indicating that direct oxygen transfer from the active oxoiron species to the sulphide is probably operative.The kinetics of the catalytic oxidation of tyrosine by hydrogen peroxide in the presence of the complex, producing the oxidative coupling dimer o,o'-dityrosine, was also studied.It is consistent with a mechanism involving the initial binding of the phenolic substrate to the active catalyst to form an intermediate complex, and its subsequent breakdown in the rate-determining step of the catalytic cycle.The results obtained in the biomimetic oxidations are compared with those of the corresponding peroxidase-catalysed reactions.

Nitric Oxide Is Reduced to HNO by Proton-Coupled Nucleophilic Attack by Ascorbate, Tyrosine, and Other Alcohols. A New Route to HNO in Biological Media?

The role of NO in biology is well established. However, an increasing body of evidence suggests that azanone (HNO), could also be involved in biological processes, some of which are attributed to NO. In this context, one of the most important and yet unanswered questions is whether and how HNO is produced in vivo. A possible route concerns the chemical or enzymatic reduction of NO. In the present work, we have taken advantage of a selective HNO sensing method, to show that NO is reduced to HNO by biologically relevant alcohols with moderate reducing capacity, such as ascorbate or tyrosine. The proposed mechanism involves a nucleophilic attack to NO by the alcohol, coupled to a proton transfer (PCNA: proton-coupled nucleophilic attack) and a subsequent decomposition of the so-produced radical to yield HNO and an alkoxyl radical. (Graph Presented).

Tyrosine nitration in peptides by peroxynitrite generated in situ in a light-controlled platform: Effects of pH and thiols

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.

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

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.

Preparation of novel HIV-protease inhibitors

The synthesis and biological properties of new HIV-1-protease inhibitors involving amino acids or dipeptides attached to binaphthol, biphenol or embonic acid are described.

The Superoxide Radical Reacts with Tyrosine-derived Phenoxyl Radicals by Addition rather than by Electron Transfer

Radiolytically generated azide radicals have been used for the formation of tyrosyl radical, TyrO, from tyrosine.The TyrO radicals combine (2k = 4.5 * 108 dm3 mol-1 s-1, determined by pulse radiolysis) yielding bityrosine in a > 90percent yield.Bityrosine formation is not suppressed in the presence of oxygen 3 dm3 mol-1 s-1>.When TyrO radical and O2 radical anion are generated side by side in a 1:1.2 ratio, bityrosine formation is strongly suppressed and (2S,3aR,7aS)- and (2S, 3aS,7aR)-3a-hydroxy-6-oxo-2,3,3a,6,7,7a-hexahydro-1H-indole-2-carboxylic acids 10 become the major final products.Their hydroperoxidic precursor is only short-liver (t1/2 = 4.2 h at room temperature and pH 8).Upon its decay H2O2 is released.Product 10 is believed to be formed by the addition of O2 radical anion to the ortho- and para-position of the phenoxyl radical, followed by protonation, ring closure and hydrolysis.Based on material balance considerations an electron transfer from O2 radical anion to TyrO radical, although thermodynamically feasible, must play a minor role ( 10percent).The rate constant k(O2 radical anion + TyrO radical) has been determined by pulse radiolysis to be 1.5 * 109 dm3 mol-1 s-1.