title: Elemental labelling and mass spectrometry for the specific detection of sulfenic acid groups in model peptides: a proof of concept.
abstract: Oxidative transformation of cysteine thiol groups into different functional groups is considered a significant posttranslational modification of great importance in pathological and physiological processes. A cysteine sulfenic acid (SA) residue is the transient state for thiol group oxidation and it can react with free thiols to form disulfide bonds or can be further oxidized with reactive oxygen/reactive nitrogen species (ROS/RNS) to form sulfinic and sulfonic acids. The increase in ROS/RNS concentrations is correlated to age-related diseases such as cancer and Alzheimer's disease. Since the formation of SA represents a transient state of oxidation of thiols, its formation can be considered a redox-sensitive sensor for the presence of ROS/RNS. Thereby, the detection of the short-lived SA will provide greater insight into the redox-mediated events that alter the structure and function of peptides and proteins. The aim of this study is to provide a new strategy for the highly sensitive and specific detection of SA in peptides as a proof of concept. For this aim, SA was firstly generated in model peptides on oxidation with H2O2and then captured by the linear alkyne β-ketoester (KE) previously linked to a lanthanide (Ln)-containing chelator (Ln-DOTA, where DOTA is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). The linking of the KE to DOTA was performed by click chemistry, resulting in a new reagent (Ln-DOTA-KE) that permits highly sensitive elemental (inductively coupled plasma) and molecular (electrospray) mass spectrometric detection. The new reagent (Ln-DOTA-KE) reacts specifically with SA, offering improved reactivity at physiological pH, facile derivatization and a cell-membrane-permeable compound that has promising future applications. Graphical Abstract A new derivatizing reagent for specific detection of sulphenic acid (SA) generated in model peptides by oxidation of cysteine groups is presented in this work.
authors.affiliation: Department of Chemistry, Humboldt University of Berlin, Brook-Taylor-Str. 2, 12489, Berlin, Germany.
authors.forename: Mona
authors.initials: M
authors.lastname: Sharar
authors.affiliation: Institute for Chemistry, Humboldt Universität zu Berlin, 12489, Berlin, Germany.|Chemistry Department, Faculty of Science, Suez Canal University, 41522, Ismailia, Egypt.
authors.forename: Essa M
authors.initials: EM
authors.lastname: Saied
authors.affiliation: Department of Physical and Analytical Chemistry, University of Oviedo, C/Julian Claveria 8, 33006, Oviedo, Spain.
authors.forename: Mario C
authors.initials: MC
authors.lastname: Rodriguez
authors.affiliation: Department of Chemistry, Humboldt University of Berlin, Brook-Taylor-Str. 2, 12489, Berlin, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Arenz
authors.affiliation: Department of Physical and Analytical Chemistry, University of Oviedo, C/Julian Claveria 8, 33006, Oviedo, Spain. montesmaria@uniovi.es.
authors.forename: Maria
authors.initials: M
authors.lastname: Montes-Bayón
authors.affiliation: Department of Chemistry, Humboldt University of Berlin, Brook-Taylor-Str. 2, 12489, Berlin, Germany. analytik@chemie.hu-berlin.de.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Linscheid
mesh_terms: D013058:Mass Spectrometry / Q000379:methods*; D008956:Models, Chemical; D010455:Peptides / Q000737:chemistry*; D013434:Sulfenic Acids / Q000737:chemistry*
chemical_list: D010455:Peptides; D013434:Sulfenic Acids
keywords: Alkyne β ketoester; Click chemistry; Elemental labelling; Sulfenic acid