Thiyl Radical Reactions in the Chemical Degradation of Pharmaceutical Proteins

Schöneich, Christian

doi:10.3390/molecules24234357

Cited by 25 publications

(16 citation statements)

References 109 publications

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“…Subsequent cleavage of the C-S bond under continued irradiation, and loss of the sulfur center via homolytic or heterolytic reactions, results in a vinylether crosslink (-C=C-O-C) [41]. It is likely that similar reactions occur with Thr residues, and analogous reactions have been detected with a Tyr in place of the Ser (reviewed in [120]).…”

Section: Sulfur-carbon (S-c) Crosslinksmentioning

confidence: 97%

“…Alternatively, photo-induced electron transfer from a photo-excited Tyr to a disulfide could occur, with this yielding Tyr • and a single RS • , with the crosslink being formed by subsequent reaction between these two species. A third potential pathway may involve addition of RS • formed from Cys B20 radical to the intact Tyr A19 residue followed by oxidation of the radical adduct [ 119 , 120 ]. The exact structure of the adduct species (i.e., whether this involves an S–O or S–C bond) remains to be resolved.…”

Section: Types Of Crosslinks Detected Within and Between Proteins And Peptidesmentioning

confidence: 99%

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Oxidative Crosslinking of Peptides and Proteins: Mechanisms of Formation, Detection, Characterization and Quantification

et al. 2021

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Covalent crosslinks within or between proteins play a key role in determining the structure and function of proteins. Some of these are formed intentionally by either enzymatic or molecular reactions and are critical to normal physiological function. Others are generated as a consequence of exposure to oxidants (radicals, excited states or two-electron species) and other endogenous or external stimuli, or as a result of the actions of a number of enzymes (e.g., oxidases and peroxidases). Increasing evidence indicates that the accumulation of unwanted crosslinks, as is seen in ageing and multiple pathologies, has adverse effects on biological function. In this article, we review the spectrum of crosslinks, both reducible and non-reducible, currently known to be formed on proteins; the mechanisms of their formation; and experimental approaches to the detection, identification and characterization of these species.

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Section: Sulfur-carbon (S-c) Crosslinksmentioning

confidence: 97%

Section: Types Of Crosslinks Detected Within and Between Proteins And Peptidesmentioning

confidence: 99%

Oxidative Crosslinking of Peptides and Proteins: Mechanisms of Formation, Detection, Characterization and Quantification

et al. 2021

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“…Thiyl radicals (RS • ), very reactive oxidants produced in the active site of enzymes such as the ribonucleotide reductase can react with nitric oxide radicals (NO • ) [ 131 ]. Thiolate ions (RS − ) are better nucleophiles than alkoxides because sulfur is more polarizable than oxygen [ 132 ].…”

Section: Oxidative Stressmentioning

confidence: 99%

Monitoring the Redox Status in Multiple Sclerosis

Tanaka

Vécsei

2020

Biomedicines

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Worldwide, over 2.2 million people suffer from multiple sclerosis (MS), a multifactorial demyelinating disease of the central nervous system. MS is characterized by a wide range of motor, autonomic, and psychobehavioral symptoms, including depression, anxiety, and dementia. The blood, cerebrospinal fluid, and postmortem brain samples of MS patients provide evidence on the disturbance of reduction-oxidation (redox) homeostasis, such as the alterations of oxidative and antioxidative enzyme activities and the presence of degradation products. This review article discusses the components of redox homeostasis, including reactive chemical species, oxidative enzymes, antioxidative enzymes, and degradation products. The reactive chemical species cover frequently discussed reactive oxygen/nitrogen species, infrequently featured reactive chemicals such as sulfur, carbonyl, halogen, selenium, and nucleophilic species that potentially act as reductive, as well as pro-oxidative stressors. The antioxidative enzyme systems cover the nuclear factor erythroid-2-related factor 2 (NRF2)-Kelch-like ECH-associated protein 1 (KEAP1) signaling pathway. The NRF2 and other transcriptional factors potentially become a biomarker sensitive to the initial phase of oxidative stress. Altered components of the redox homeostasis in MS were discussed in search of a diagnostic, prognostic, predictive, and/or therapeutic biomarker. Finally, monitoring the battery of reactive chemical species, oxidative enzymes, antioxidative enzymes, and degradation products helps to evaluate the redox status of MS patients to expedite the building of personalized treatment plans for the sake of a better quality of life.

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“…Thiyl radicals (RS • ), very reactive oxidants produced in the active site of enzymes such as the ribonucleotide reductase can react with nitric oxide radicals (NO • ) [88]. Thiolate ions (RS − ) are better nucleophiles than alkoxides because sulfur is more polarizable than oxygen [89].…”

Section: Reactive Sulfur Speciesmentioning

confidence: 99%

Monitoring the Redox Status in Multiple Sclerosis

Tanaka¹,

Vécsei²

2020

Preprint

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Worldwide, over 2.2 million people are suffered from multiple sclerosis (MS), a multifactorial demyelinating disease of the central nervous system, characterized by multifocal inflammatory or demyelinating attacks associated with neuroinflammation and neurodegeneration. The blood, cerebrospinal fluid, and postmortem brain samples of MS patients evidenced the presence of reduction-oxidation (redox) homeostasis disturbance such as the alternations of oxidative and antioxidative enzyme activities and the presence of degradation products. This review article discussed the components of redox homeostasis including reactive chemical species, oxidative enzymes, antioxidative enzymes, and degradation products. The reactive chemical species covered frequently discussed reactive oxygen/nitrogen species, rarely featured reactive chemicals such as sulfur, carbonyls, halogens, selenium, and nucleophilic species that potentially act as reductive as well as pro-oxidative stressors. The antioxidative enzyme systems covered the nuclear factor erythroid-2-related factor 2 (NRF2)-Kelch-like ECH-associated protein 1 (KEAP1) signaling pathway, a possible biomarker sensitive to the initial phase of oxidative stress. Altered components of the redox homeostasis in MS were discussed, some of which turned to be MS subtype- or treatment-specific and thus potentially become diagnostic, prognostic, predictive, and/or therapeutic biomarkers. Finally, monitoring a battery of redox components including oxidative, antioxidative and degradation products helps evaluate the redox status of MS patients, which expedites prolongation of remission, relapse prevention, and building personalized treatment plans.

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Thiyl Radical Reactions in the Chemical Degradation of Pharmaceutical Proteins

Cited by 25 publications

References 109 publications

Oxidative Crosslinking of Peptides and Proteins: Mechanisms of Formation, Detection, Characterization and Quantification

Oxidative Crosslinking of Peptides and Proteins: Mechanisms of Formation, Detection, Characterization and Quantification

Monitoring the Redox Status in Multiple Sclerosis

Monitoring the Redox Status in Multiple Sclerosis

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