Publications related to Probing Cysteine Reactivity in Proteins by Mass Spectrometric EC-Tagging

Amphiphilic Iodine(III) Reagents for the Lipophilization of Peptides in Water

Jérôme Waser, Durga Prasada Rao Hari, Romain Gaëtan Tessier, Abhaya Kumar Mishra

We report the functionalization of cysteine residues with lipophilic alkynes bearing a silyl group or an alkyl chain using amphiphilic ethynylbenziodoxolone reagents (EBXs). The reactions were carried out in buffer (pH 6 to 9), without organic co-solvent o ...

Wiley-VCH Verlag GmbH2021

Ethynylation of Cysteine Residues: From Peptides to Proteins in Vitro and in Living Cells

Jérôme Waser, Charlotte Marie Sornay, Romain Gaëtan Tessier, Raj Kumar Nandi

Current approaches to introduce terminal alkynes for bioorthogonal reactions into biomolecules still present limitations in terms of either reactivity, selectivity, or adduct stability. We present a method for the ethynylation of cysteine residues based on ...

Wiley-VCH Verlag GmbH2020

Application of Hypervalent Iodine Reagents for Novel Cysteine Labeling

Romain Gaëtan Tessier

Selective functionalization of peptides and proteins has always been a valuable tool for the study and manipulation of biological processes. In this context, cysteines are of particular interest. Their intrinsic high nucleophilicity makes these amino acids ...

EPFL2019

Discovery of novel competitive dihydropteridine reductase inhibitors via high throughput screening and their effect on metabolic pterin balance of fibroblast

Yann Mathieu Pierson

The development of tool compounds for the study of the tetrahydrobiopterin (BH4) metabolic network perturbation is of interest especially in the case of oxidative and nitrosative stress genesis. A semisynthetic FRET sensor was engineered in order to study ...

EPFL2018

Transition metal clusters on h-BN/Rh(111) : surface interaction and catalytic activity

Hamed Achour

The main aim of this dissertation is to study the catalytic aspects of very small transition metal clusters supported on h-BN/Rh(111). The catalytic reactions of interest were ammonia synthesis and CO oxidation on mass selected and soft landed iron and pla ...

EPFL2017

Top-down analysis of immunoglobulin G isotypes 1 and 2 with electron transfer dissociation on a high-field Orbitrap mass spectrometer

Yury Tsybin, Luca Fornelli, Daniel Ayoub

The increasing importance of immunoglobulins G (IgGs) as biotherapeutics calls for improved structural characterization methods designed for these large (similar to 150 kDa) macromolecules. Analysis workflows have to be rapid, robust, and require minimal s ...

Elsevier Science Bv2017

Middle-down approaches for mass spectrometry-based protein identification and characterization

Kristina Srzentic

Mass spectrometry (MS) has emerged over the last two decades as the analytical technique of choice in systems-level protein studies, known as proteomics. Two are the MS-based approaches generally applied to proteomics: bottom-up (BU), which relies on the p ...

EPFL2016

Development of mass spectrometric methods to understand the mechanism of action of transition metal-based anticancer compounds

Fook Seng Ronald Lee

Metal based anti-cancer drugs (metallodrugs) such as cisplatin are a cornerstone of cancer chemotherapy. However, development of this class of compound has been hindered by our lack of understanding of how they function. This is mainly because existing met ...

EPFL2016

Discovery of benzothiazoles as antimycobacterial agents: Synthesis, structure-activity relationships and binding studies with Mycobacterium tuberculosis decaprenylphosphoryl-beta-D-ribose 2 '-oxidase

Stewart Cole, Florence Pojer, Anirban Ghosh, Joao Pedro De Almeida Neres

We report the discovery of benzothiazoles, a novel anti-mycobacterial series, identified from a whole cell based screening campaign. Benzothiazoles exert their bactericidal activity against Mycobacterium tuberculosis (Mtb) through potent inhibition of deca ...

Elsevier2015

Dithiol amino acids can structurally shape and enhance the ligand-binding properties of polypeptides

Rudolf Hovius, Christian Heinis, Florence Pojer, Shiyu Chen, Ranganath Gopalakrishnan

The disulfide bonds that form between two cysteine residues are important in defining and rigidifying the structures of proteins and peptides. In polypeptides containing multiple cysteine residues, disulfide isomerization can lead to multiple products with ...

Nature Publishing Group2014

Extended Bottom-Up Proteomics with Secreted Aspartic Protease Sap9

Yury Tsybin, Unige Anna Laskay, Kristina Srzentic

We investigate the benefits and experimental feasibility of approaches enabling the shift from short (1.7 kDa on average) peptides in bottom-up proteomics to about twice longer (similar to 3.2 kDa on average) peptides in the so-called extended bottom-up pr ...

Elsevier Science Bv2014

Spectroscopic studies of peptide fragments produced by collision-induced dissociation

Oleg Aseev

Tandem mass spectrometry (MS/MS) combined with collision-induced dissociation (CID) is a key method for primary structure determination of peptides and proteins. Collisionally activated peptides undergo statistical dissociation, forming a series of backbon ...

EPFL2014

Development of New Bicyclic Peptide Formats and their Application in Directed Evolution

Shiyu Chen

Cyclic peptides have a range of properties that make them attractive as therapeutics such as high binding affinity, good target selectivity and low toxicity. While most peptides in the clinic are derived from nature, various powerful in vitro evolution tec ...

EPFL2013

UV radiation induces genome-mediated, site-specific cleavage in viral protein

Hisham Ben Hamidane, Anne Thérèse Sigstam, Michele Cascella, Tamar Kohn, Yury Tsybin, Laure Menin, Krista Rule Wigginton

Much research has been dedicated to understanding the molecular basis of UV damage to biomolecules, yet many questions remain regarding the specific pathways involved. Here we describe a genome-mediated mechanism that causes sitespecific virus protein clea ...

2012

Fragmentation methods on the balance: unambiguous top–down mass spectrometric characterization of oxaliplatin–ubiquitin binding sites

Paul Joseph Dyson, Yury Tsybin, Christian Hartinger

The interaction between oxaliplatin and the model protein ubiquitin (Ub) was investigated in a top-down approach by means of high-resolution electrospray ionization mass spectrometry (ESI-MS) using diverse tandem mass spectrometric (MS/MS) techniques, incl ...

Springer-Verlag2012

Small Molecule Based Approaches to Inhibit Macrophage Migration Inhibitory Factor (MIF) Activities and Elucidate its Role in Health and Disease

Hajer Ouertatani-Sakouhi

Macrophage migration inhibitory factor (MIF) is a major mediator in innate immunity and inflammation and a potential therapeutic target in multiple inflammatory, infectious and autoimmune diseases including cancer. Current therapeutic strategies for target ...

EPFL2010

The role of copper in cysteine oxidation: study of intra- and inter-molecular reactions in mass spectrometry

Hubert Girault, Michel Prudent

Cysteine-containing peptide oxidation was studied both by using an inert platinum electrode and a sacrificial electrode (copper or zinc) generating metallic ions in electrospray ionization mass spectrometry (ESI-MS). Using peptides containing one, two and ...

Royal Society of Chemistry2009

Electrospray ionization mass spectrometry : electrochemistry and on-chip reactions for bioinorganic analyses

Michel Prudent

Metal ions are essential elements in all living systems. Their detections and identifications in biological processes require different methodologies. Mass spectrometry is one of the commonly used techniques in bioinorganic analyses to fulfill these requir ...

EPFL2009

High Resolution Mass Spectrometry for Studying the Interactions of Cisplatin with Oligonucleotides

Hisham Ben Hamidane, Paul Joseph Dyson, Yury Tsybin, Christian Hartinger

Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) has been used to probe the interaction of the anticancer drug cisplatin with oligonucleotides. The binding kinetics, the nature of the adducts formed, and the location of the binding s ...

2008

Thiol-targeted microspray mass spectrometry of peptides and proteins through on-line EC-tagging

Loïc Dayon

Modification strategies targeting specific amino acids in proteins are widespread in proteomic analysis. Cysteine residues have received deep consideration in view of their nucleophilic properties and their occurrence in the proteome. A recently developed ...

EPFL2006