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

deBoer, Tara R.; Palomino, Rafael; Idiga, Sharon O.; Millhauser, Glenn L.; Mascharak, Pradip K.

doi:10.1016/j.jinorgbio.2014.04.018

Cited by 5 publications

(3 citation statements)

References 48 publications

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“…Peroxynitrite-generating platforms were constructed as described in our previous publication [8,13]. In short, individual NO · and O 2 ·− generating sol-gel pieces were synthesized through the encapsulation of [Mn(PaPy 3 )(NO)]ClO 4 (PaPy 3 = N , N ′-bis(2-pyridylmethylamine)- N -ethyl-2-pyridine-2-carboxamide) or XO and CAT solutions into respective tetramethylorthosilicate matrices.…”

Section: Methodsmentioning

confidence: 99%

“…0.600 mL aliquots of the metal nitrosyl sol-gel solution and 0.800 mL aliquots of the XO-CAT sol-gel were then transferred into their corresponding plates and allowed to solidify and dry in the dark for 1 week at 4 °C. Activity of the final sol-gel pieces were analyzed at random prior to use [8,13]. The individual sol-gel pieces were then combined into single wells of a 24-well plate to afford the final PN-generating system that affords ~4 μM min −1 fluxes of PN.…”

Section: Methodsmentioning

confidence: 99%

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Peroxynitrite-Mediated Dimerization of 3-Nitrotyrosine: Unique Chemistry along the Spectrum of Peroxynitrite-Mediated Nitration of Tyrosine

deBoer

Palomino

Mascharak

2019

Med One

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Peroxynitrite (ONOO − , PN) has long been considered a potent nitrating agent implicated in numerous inflammation-mediated diseases. The current work highlights an unexplored oxidation chemistry initiated under conditions of sustained PN exposure. Impetus for this investigation developed from mass spectral results that suggested dimerization of a model peptide with a single tyrosine residue that was first nitrated following extended exposure to PN generated in situ . In attempts to substantiate this dimerization event and divulge the possible mode of linkage between the tyrosine derivatives of the peptide monomers, 3-nitrotyrosine (3-NT) was exposed to sustained fluxes of PN in a two-component PN-generating platform developed in this laboratory. Such exposure afforded products with tandem mass spectrometry and fluorescence spectroscopy profiles indicative of C–O coupling between 3-NT moieties. Synthesis and comparative analysis of the C–C coupled 3-NT isomer corroborated these findings. Most notably, the mass spectral data of the C–C coupled 3-NT dimer displayed a 226.80 m/z peak following exposure to high collision energy, corresponding to symmetric cleavage of the parent dimer peak ( m/z = 453) along with a fragmentation product at m/z = 180.04 (–NO 2 species). This fragmentation profile was distinct from the C–O coupled 3-NT dimer that exhibited a predominant 209.14 m/z peak with a small secondary 226.15 m/z peak indicative of asymmetric cleavage of the parent dimer. Results of this study indicate that formation of C–O coupled 3-NT dimer is promoted by elevated levels of 3-NT formed under high and sustained flux of PN.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Peroxynitrite-Mediated Dimerization of 3-Nitrotyrosine: Unique Chemistry along the Spectrum of Peroxynitrite-Mediated Nitration of Tyrosine

deBoer

Palomino

Mascharak

2019

Med One

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“…Furthermore, such agents activate a large number of signaling and metabolic cascades in parallel with NO or O 2 •– generation. Two component systems which can generate O 2 •– using a small molecule or hypoxanthine/xanthine oxidase in conjunction with an exogenous NO donor such as a diazeniumdiolate or a metal (NO) complex have been successfully used to produce ONOO – . − These protocols efficiently generate ONOO – and are well suited for biochemical studies, but little evidence for their utility in cellular assays is available . The most commonly used ONOO – donor for cellular studies, 3-morpholino syndnonimine (SIN-1), is a mesionic heterocyclic aromatic compound and forms peroxynitrite through a complex mechanism and offers no control over ONOO – production. , Recently, photochemically activated peroxynitrite generators have been reported. , Although spatiotemporal control over ONOO – generation is achieved, the use of an external light source may not always be convenient for cell-based studies.…”

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confidence: 99%

A Small Molecule for Controlled Generation of Peroxynitrite

et al. 2016

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2-Methyl-3-[1-(N,N-dimethylamino)diazen-1-ium-1,2-diol-2-ato-methyl]-naphthalene-1,4-dione 1 (HyPR-1), a small molecule containing a superoxide generator strategically linked to a diazeniumdiolate-based nitric oxide donor, is reported. Evidence for HyPR-1's ability to generate peroxynitrite in the presence of an enzyme as well as enhance peroxynitrite within cells is provided. The utility of this tool in generating peroxynitrite for cellular studies is demonstrated.

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A Carbon‐Caged Rhodamine Generating Nitrosoperoxycarbonate for Photoimmunotherapy

Yin,

Zhao,

Zhou

et al. 2024

Angewandte Chemie

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Photoimmunotherapy is a promising cancer treatment modality. While potent 1‐e‐ oxidative species are known to induce immunogenic cell death (ICD), they are also associated with unspecific oxidation and collateral tissue damage. This difficulty may be addressed by post‐generation radical reinforcement. Namely, non‐oxidative radicals are first generated and subsequently activated into powerful oxidative radicals to induce ICD. Here, we developed a photo‐triggered molecular donor (NPCD565) of nitrosoperoxycarbonate (ONOOCO2‐), the first of its class to our knowledge, and further evaluated its feasibility for immunotherapy. Upon irradiation of NPCD565 by light within a broad spectral region from ultraviolet to red, ONOOCO2‐ is released along with a bright rhodamine dye (RD565), whose fluorescence is a reliable and convenient build‐in reporter for the localization, kinetics, and dose of ONOOCO2‐ generation. Upon photolysis of NPCD565 in 4T1 cells, damage‐associated molecular patterns (DAMPs) indicative of ICD were observed and confirmed to exhibit immunogenicity by induced maturation of dendritic cells. In vivo studies with a bilateral tumor‐bearing mouse model showcased the potent tumor‐killing capability of NPCD565 of the primary tumors and growth suppression of the distant tumors. This work unveils the potent immunogenicity of ONOOCO2‐, and its donor (NPCD565) has broad potential for photo‐immunotherapy of cancer.

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

Cited by 5 publications

References 48 publications

Peroxynitrite-Mediated Dimerization of 3-Nitrotyrosine: Unique Chemistry along the Spectrum of Peroxynitrite-Mediated Nitration of Tyrosine

Peroxynitrite-Mediated Dimerization of 3-Nitrotyrosine: Unique Chemistry along the Spectrum of Peroxynitrite-Mediated Nitration of Tyrosine

A Small Molecule for Controlled Generation of Peroxynitrite

A Carbon‐Caged Rhodamine Generating Nitrosoperoxycarbonate for Photoimmunotherapy

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