Proteome‐Wide Survey of Cysteine Oxidation by Using a Norbornene Probe

Alcock, Lisa J; Langini, Maike; Remke, Marc; Perkins, Michael V.; Bernardes, Gonçalo J. L.; Chalker, Justin M.

doi:10.1002/cbic.201900729

Cited by 12 publications

(9 citation statements)

References 42 publications

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“…For the identification of such proteins, a set of approaches and tools have been developed over recent years [162,163]. Using specific probes, changes in HSC sulfenome/sulfinome during cell activation have been identified [164,165]. Besides identifying key redox-dependent players in fibrogenesis, these approaches may also allow estimating the input of various ROS sources into the fibrogenic process by analyzing their proximity to redox switches.…”

Section: Redox Biologymentioning

confidence: 99%

Metabolic Hallmarks of Hepatic Stellate Cells in Liver Fibrosis

Khomich

Ivanov

Bartosch

2019

Cells

134

154

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Liver fibrosis is a regenerative process that occurs after injury. It is characterized by the deposition of connective tissue by specialized fibroblasts and concomitant proliferative responses. Chronic damage that stimulates fibrogenic processes in the long-term may result in the deposition of excess matrix tissue and impairment of liver functions. End-stage fibrosis is referred to as cirrhosis and predisposes strongly to the loss of liver functions (decompensation) and hepatocellular carcinoma. Liver fibrosis is a pathology common to a number of different chronic liver diseases, including alcoholic liver disease, non-alcoholic fatty liver disease, and viral hepatitis. The predominant cell type responsible for fibrogenesis is hepatic stellate cells (HSCs). In response to inflammatory stimuli or hepatocyte death, HSCs undergo trans-differentiation to myofibroblast-like cells. Recent evidence shows that metabolic alterations in HSCs are important for the trans-differentiation process and thus offer new possibilities for therapeutic interventions. The aim of this review is to summarize current knowledge of the metabolic changes that occur during HSC activation with a particular focus on the retinol and lipid metabolism, the central carbon metabolism, and associated redox or stress-related signaling pathways.Most of the progress that has been made in the identification of the molecular mechanisms underlying fibrosis is based on the use of in vitro model systems using tissue culture-adapted HSC lines, primary HSC preparations, and a number of in vivo models such as animals being fed high-fat/cholesterol or choline-deficient diets, animals that undergo bile duct ligation, treatment with ethanol, CCl 4 or other chemical agents, or transgenic animals [5]. Hepatic Stellate CellsThe cell type that is predominantly responsible for fibrotic processes is hepatic stellate cells (HSCs), a mesenchymal cell population that constitutes 5-10% of the total number of cells in the liver (Figure 1). HSCs are located in the perisinusoidal space (space of Disse) and are surrounded by hepatocytes and sinusoidal endothelial cells [6,7]. Their main functions are the secretion of laminin, proteoglycans, and type IV collagen to form basement membrane-like structures. Quiescent HSCs start to proliferate and undergo trans-differentiation into contractile myofibroblasts in response to paracrine stimulation by neighboring cell types, including Kupffer cells, hepatocytes, platelets, leukocytes, and sinusoidal endothelial cells. Kupffer cells can stimulate activation and proliferation of HSCs through the actions of cytokines, and in particular transforming growth factor β1 (TGFβ1), interleukin 1 (IL-1), tumor necrosis factor (TNF), reactive oxygen species (ROS) and lipid peroxides [6,8]. Hepatocytes are an important source of inflammatory lipid peroxides in liver diseases. Platelets release pro-fibrogenic growth factors such as platelet-derived growth factor (PDGF), TGFβ1, and epidermal growth factor (EGF). Neutrophils are an important source of RO...

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Section: Redox Biologymentioning

confidence: 99%

Metabolic Hallmarks of Hepatic Stellate Cells in Liver Fibrosis

Khomich

Ivanov

Bartosch

2019

Cells

134

154

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“…Last but not least, we address the potential cross-reactivity with a ubiquitous reactive oxygen species, hydrogen peroxide (H 2 O 2 ), which is also an electrophile. It has been reported that dimedone underwent oxidative dimerization when exposed to excessive (high millimolar) concentrations of H 2 O 2 [ 45 ]. However, the impact of this reaction is unclear under practical labeling conditions.…”

Section: Resultsmentioning

confidence: 99%

Parallel evaluation of nucleophilic and electrophilic chemical probes for sulfenic acid: Reactivity, selectivity and biocompatibility

Shi

Carroll

2021

Redox Biology

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Cysteine sulfenic acids (Cys-SOH) are pivotal modifications in thiol-based redox signaling and central intermediates en route to disulfide and sulfinic acid states. A core mission in our lab is to develop bioorthogonal chemical tools with the potential to answer mechanistic questions involving cysteine oxidation. Our group, among others, has contributed to the development of nucleophilic chemical probes for detecting sulfenic acids in living cells. Recently, another class of Cys-SOH probes based on strained alkene and alkyne electrophiles has emerged. However, the use of different models of sulfenic acid and methodologies, has confounded clear comparison of these probes with respect to chemical reactivity, kinetics, and selectivity. Here, we perform a parallel evaluation of nucleophilic and electrophilic chemical probes for Cys-SOH. Among the key findings, we demonstrate that a probe for Cys-SOH based on the norbornene scaffold does not react with any of the validated sulfenic acid models in this study. Furthermore, we show that purported cross-reactivity of dimedone-like probes with electrophiles, like aldehydes and cyclic sulfenamides, is a not meaningful in a biological setting. In summary, nucleophilic probes remain the most viable tools for bioorthogonal detection of Cys-SOH.

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“…Proteomic analysis of the labeled proteins revealed 148 new protein members of the sulfenome, evidently showing that these norbornene-based probes are complementary to previously reported probes. 180 One of the latest developments utilizes the reactivity of sulfenic acid modifying trans-cyclooctenol (SAM-TCO) derivative (such as 95) that (i) contains a strained E-alkene that reacts with sulfenic acid to form [3.3.1]oxabicycle 97 after intramolecular nucleophilic attack and ring opening of 96, (ii) facilitates in situ quench of the remaining SAM-TCO 95 with a methyltetrazine (MeTz) derivative, and (iii) contains an alkyne as handle for secondary labeling of the reacted sulfenic acidcontaining proteins by means of CuAAC to form biotin-labeled product 97, for example. 181 The combination of the high in vitro reaction rate of 95 and sulfenic acids of 750 M −1 •s −1 and the even higher reaction rate constants of the IEEDA between 95 and MeTz enable time-resolved chemoproteomic profiling of sulfenylation in cell lysates.…”

Section: Cysteinementioning

confidence: 99%

Oxidation-Induced “One-Pot” Click Chemistry

et al. 2021

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Click chemistry has been established rapidly as one of the most valuable methods for the chemical transformation of complex molecules. Due to the rapid rates, clean conversions to the products, and compatibility of the reagents and reaction conditions even in complex settings, it has found applications in many molecule-oriented disciplines. From the vast landscape of click reactions, approaches have emerged in the past decade centered around oxidative processes to generate in situ highly reactive synthons from dormant functionalities. These approaches have led to some of the fastest click reactions know to date. Here, we review the various methods that can be used for such oxidation-induced “one-pot” click chemistry for the transformation of small molecules, materials, and biomolecules. A comprehensive overview is provided of oxidation conditions that induce a click reaction, and oxidation conditions are orthogonal to other click reactions so that sequential “click-oxidation-click” derivatization of molecules can be performed in one pot. Our review of the relevant literature shows that this strategy is emerging as a powerful approach for the preparation of high-performance materials and the generation of complex biomolecules. As such, we expect that oxidation-induced “one-pot” click chemistry will widen in scope substantially in the forthcoming years.

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Proteome‐Wide Survey of Cysteine Oxidation by Using a Norbornene Probe

Cited by 12 publications

References 42 publications

Metabolic Hallmarks of Hepatic Stellate Cells in Liver Fibrosis

Metabolic Hallmarks of Hepatic Stellate Cells in Liver Fibrosis

Parallel evaluation of nucleophilic and electrophilic chemical probes for sulfenic acid: Reactivity, selectivity and biocompatibility

Oxidation-Induced “One-Pot” Click Chemistry

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