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 Accueil > Équipes > Chimie Bio-inorganique des Dérivés Soufrés et Pharmacochimie > Research > Chemical Biology and Molecular Tools for Sulfur Metabolic Compounds.

 

Chemical Biology and Molecular Tools for Sulfur Metabolic Compounds.

Par Assia - 6 octobre 2014

 

 

E. Galardon, D. Padovani, Isabelle Artaud, M. Dulac (PhD 2015-2018)

 

 Collaborators :

Dr. V. Baland (LEM - Université Paris 7 - Comue SPC), Dr. F. Blachier & Dr. A. Lan (AgroParisTech), Dr. F. Bouillaud - Institut Cochin - Comue SPC), Dr. B. Chadefaux-Vekemans), Dr. X. Norel (Hôpital Bichat - Université Paris Nord), Pr. Dr. P. Hildebrandt (Technische Universität Berlin, Germany), Dr. B. Kloesh (Ludwig Boltzmann Institute for Rheumatology, Balneology and Rehabilitation, Vienna, Austria)

 

 

Scientific context

 

Methionine metabolism furnishes cells with important sulfur metabolic compounds, e.g. S-adenosylmethionine (SAM), glutathione (GSH), taurine, cysteine (Cys) and hydrogen sulfide (H2S) (Figure). H2S is a small gaseous molecule endogeneously produced mainly by two enzymes from the transsulfuration pathway, cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE) (Figure). It emerges, along with nitric oxide NO and carbon monoxide CO, as a new gaseous signaling molecule in mammals. H2S exerts important functions in the cardiovascular system and the central nervous system and is an endogenous regulator of inflammatory response. Under physiological conditions, it exist as a mixture of the neutral hydrophobic H2S and the charged hydrophilic HS- (pKa = 6.78 at pH 7.4 and 37°C). Added to its small size, this grants him access to various metal ions localized in proteins active site, and could mediate some of H2S diverse biological effects. H2S may also signal through interaction with NO and formation of thionitrous acid (HSNO) or nitrosopersulfide (SSNO-), appears to modulate targeted proteins activity through persulfide formation, and is involved in second messenger electrophilic signaling.

 

http://www.biomedicale.univ-paris5.fr/umr8601/IMG/jpg/T3.jpg

 

 

All the above-mentioned reactions involve oxidation of H2S, which like biological thiols can act as pro-oxidant (dashed-bold arrows). Therefore, their metabolism is strongly regulated, but the impairment of redox-based signaling under oxidative stress conditions induces a shift in thiol/redox signaling pathways such as thiyl radicals formation as precursors of irreversible protein damage, glutathioniyl radicals generation, autoxidation of H2S contributing to DNA damage,..., often associated with severe pathologies.

 

 

In this context, in collaboration with biologists sharing our interest in H2S, we use various techniques (biochemistry, organic and bioinorganic chemistry, analytical methods) to :

 

(i) explore the biological and bio-inorganic chemistry of sulfur compounds in the context of H2S signaling

(ii) explore the impact of pathological conditions on H2S biogenesis or RSH/H2S toxicity

(iii) develop analytical and chemical tools to investigate the role of H2S in biology

 

 

 

Recent publications

 

Sulfheme formation during homocysteine S-oxygenation by catalase in cancers and neurodegenerative diseases.

Padovani D., Hessani A., Castillo F. T., Liot G., Andriamihaja M., Lan A., Pilati C., Blachier F., Sen S., Galardon E. & Artaud I..

Nat. Commun. 2016, 7, 13386.  

 

Improved tag-switch method reveals that thioredoxin acts as depersulfidase and controls the intracellular levels of protein persulfidation

Wedmann R, Onderka C, Wei S, Szijártó IA, Miljkovic JL, Mitrovic A, Lange M, Savitsky S, Yadav PK, Torregrossa R, Harrer EG, Harrer T, Ishii I, Gollasch M, Wood ME, Galardon E, Xian M, Whiteman M, Banerjee R, Filipovic M.R

Chem. Sci. . 2016, May 25 ;7(5):3414-3426.  

 

Reactivity of Persulfides Towards Strained Bicyclo[6.1.0]nonyne Derivatives : Relevance to Chemical Tagging of Proteins. 

E. Galardon, D. Padovani

Bioconj. Chem., 2015, 26, 1013-1016  

 

 A Persulfide Analog of the Nitrosothiol SNAP : Formation, Characterization and Reactivity. 

I. Artaud, E. Galardon

ChemBioChem, 2014, 15(16), 2361- 4, also see : Nat. Chem. Biol, 2014, 10,876

 

 Electrophilic Sulfhydration of 8-nitro-cGMP Involves Sulfane Sulfur 

V. Terzic, D. Padovani, V. Balland, I. Artaud, E. Galardon

Org. Biomol. Chem, 2014, 12, 5360-5364

 

New Biologically Active H2S Donors 

 T. Roger, F. Raynaud , F. Bouillaud, C. Ransy, S. Simonet, C. Crespo, M.-P. Bourguignon, N. Villeneuve, J.-P. Vilaine, I. Artaud, E. Galardon

 ChemBioChem, 2013, 14,2268-2271

 

 

 

 

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