Norbornene Probes for the Detection of Cysteine Sulfenic Acid in Cells

Alcock, Lisa J; Oliveira, Bruno L.; Deery, Michael J.; Pukala, Tara L.; Perkins, Michael V.; Bernardes, Gonçalo J. L.; Chalker, Justin M.

doi:10.1021/acschembio.8b01104

Cited by 39 publications

(40 citation statements)

References 27 publications

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“…Additionally,t he norbornene moiety couldp otentially be used in other labeling reactions. [38,39] These results demonstratet he potential of this methodology for the tailoringo fR iPPs.…”

Section: Introductionmentioning

confidence: 62%

Selective Modification of Ribosomally Synthesized and Post‐Translationally Modified Peptides (RiPPs) through Diels–Alder Cycloadditions on Dehydroalanine Residues

Vries

Viel

Oudshoorn

et al. 2019

Chemistry A European J

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We report the late‐stage chemical modification of ribosomally synthesized and post‐translationally modified peptides (RIPPs) by Diels–Alder cycloadditions to naturally occurring dehydroalanines. The tail region of the thiopeptide thiostrepton could be modified selectively and efficiently under microwave heating and transition‐metal‐free conditions. The Diels–Alder adducts were isolated and the different site‐ and endo/exo isomers were identified by 1D/2D 1H NMR. Via efficient modification of the thiopeptide nosiheptide and the lanthipeptide nisin Z the generality of the method was established. Minimum inhibitory concentration (MIC) assays of the purified thiostrepton Diels–Alder products against thiostrepton‐susceptible strains displayed high activities comparable to that of native thiostrepton. These Diels–Alder products were also subjected successfully to inverse‐electron‐demand Diels–Alder reactions with a variety of functionalized tetrazines, demonstrating the utility of this method for labeling of RiPPs.

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“…Additionally,t he norbornene moiety couldp otentially be used in other labeling reactions. [38,39] These results demonstratet he potential of this methodology for the tailoringo fR iPPs.…”

Section: Introductionmentioning

confidence: 62%

Selective Modification of Ribosomally Synthesized and Post‐Translationally Modified Peptides (RiPPs) through Diels–Alder Cycloadditions on Dehydroalanine Residues

Vries

Viel

Oudshoorn

et al. 2019

Chemistry A European J

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“…Proteins sensitive to ROS-mediated post-translational modifications are often referred to as redox switches. 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].…”

Section: Redox Biologymentioning

confidence: 99%

Metabolic Hallmarks of Hepatic Stellate Cells in Liver Fibrosis

Khomich

Ivanov

Bartosch

2019

Cells

160

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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“…As laid out in the original cycle, the reduction of sulfenic acid also needs to be tested as an essential path back to the thiol (Figure ). Sulfenic acids are highly reactive molecules that are very difficult to isolate or even detect . Therefore, we used the elimination of sulfoxide 4 and sulfone 5 by DBU to generate sulfenic acid in situ, followed by reduction using added triphenylphosphine (PPh 3 ) without intermediate purification.…”

Section: Figurementioning

confidence: 99%

“…Sulfenic acids are highly reactive molecules that are very difficult to isolate or even detect. [30] Therefore, we used the elimination of sulfoxide 4 and sulfone 5 by DBU to generate sulfenic acid in situ, followed by reduction using added triphenylphosphine (PPh 3 ) without intermediate purification. The mixture was stirred overnight at room temperature, after which it was analyzed by 1 H NMR ( Figure S13).…”

Section: Communicationsmentioning

confidence: 99%

A Fuel‐Driven Chemical Reaction Network Based on Conjugate Addition and Elimination Chemistry

et al. 2019

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Fuel‐driven chemical reaction networks provide an opportunity to develop chemical systems that operate out‐of‐equilibrium. There remains a need to design and develop new fuel‐driven chemical reaction networks capable of repeated operation using simple and benign chemistry. Herein, we propose a new chemical reaction network for fuel‐driven transient formation of covalent bonds, based on redox‐controlled conjugate addition and elimination chemistry. By investigating the separate reactions making up the cycle, we find that the bond formation, breaking and regeneration processes can be realized. At present, substantial side reactivity prevents achieving repeated operation of a full cycle in a single system. If such obstacles would be overcome, this chemical reaction network could be a valuable addition to the toolbox for out‐of‐equilibrium systems chemistry.

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Norbornene Probes for the Detection of Cysteine Sulfenic Acid in Cells

Cited by 39 publications

References 27 publications

Selective Modification of Ribosomally Synthesized and Post‐Translationally Modified Peptides (RiPPs) through Diels–Alder Cycloadditions on Dehydroalanine Residues

Selective Modification of Ribosomally Synthesized and Post‐Translationally Modified Peptides (RiPPs) through Diels–Alder Cycloadditions on Dehydroalanine Residues

Metabolic Hallmarks of Hepatic Stellate Cells in Liver Fibrosis

A Fuel‐Driven Chemical Reaction Network Based on Conjugate Addition and Elimination Chemistry

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