Chemical methods for mapping cysteine oxidation

Abstract

Cysteine residues in proteins are subject to diverse redox chemistry. Oxidation of cysteine to S-nitrosocysteine, cysteine sulfenic and sulfinic acids, disulfides and persulfides are a few prominent examples of these oxidative post-translational modifications. In living organisms, these modifications often play key roles in cell signalling and protein function, but a full account of this biochemistry is far from complete. It is therefore an important goal in chemical biology to identify what proteins are subjected to these modifications and understand their physiological function. This review provides an overview of these modifications, how they can be detected and quantified using chemical probes, and how this information provides insight into their role in biology. This survey also highlights future opportunities in the study of cysteine redox chemistry, the challenges that await chemists and biologists in this area of study, and how meeting such challenges might reveal valuable information for biomedical science.

Metabolic Hallmarks of Hepatic Stellate Cells in Liver Fibrosis

“…In recent years, many lines of evidence point to the biological impact of ROS on enzymatic functions via modification of cysteine residues. A list of redox post-translational cysteine modifications includes oxidation into sulfenic and later into sulfinic and sulfonic acids, S-glutathionylation, nitration (nitrosylation), and others [162]. Proteins sensitive to ROS-mediated post-translational modifications are often referred to as redox switches.…”

“…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].…”

Proteome‐Wide Analysis of Cysteine S‐Sulfenylation Using a Benzothiazine‐Based Probe

“…However, the moderate reactivity of the dimedone warhead towards cysteine sulfenic acid prevents its utility in proteomic application in two‐fold: (1) an extremely large amount of input (20 to 30 mg) and experimental materials (e.g., sequencing‐grade trypsin, desalting columns, SCX spin columns) are required, and (2) labeling reactions mediated by the dimedone‐based probe cannot overcompete with the rapid turnover of many cysteine sulfenic acids during in situ and in vitro labeling of cell or tissue samples. In addition to dimedone, many other types of chemistry have been explored to selectively label S‐sulfenic acids (Alcock, Perkins, & Chalker, ; McGarry, Shchepinova, Lilla, Hartley, & Olson, ; Poole et al., ; Qian et al., ). However, none has been applied to global and site‐specific analysis of this modification.…”

Upper‐Rim Monofunctionalisation in the Synthesis of Triazole‐ and Disulfide‐Linked Multicalix[4]‐ and ‐[6]arenes

“…Cysteine is an important thiol‐containing α‐amino acid and is a component of the bioactive peptide glutathione (biomarker of cell oxidative stress). Both readily undergo redox chemistry.…”

“…Cysteine is an important thiol-containing a-aminoa cid [43] and is ac omponent of the bioactive peptideg lutathione (biomarker of cell oxidative stress [44] ). Both readily undergo redox chemistry.T hus cysteine and glutathione when oxidised are transformed into homodimeric SÀSl inked cystine [45] and glutathione disulfide (GSSG) [44b, 46] (not shown), respectively.C onfident in our ability to generate redox-active calix[4]arene-based multi-calixarenes cf.…”