Biological Chemistry
The team BIOLOGICAL CHEMISTRY is a multidisciplinary team composed of chemists, biochemists and immunologist who share common strategies related to protein chemistry and reactivity. Its activity involves chemical synthesis, protein chemistry, redox (bio)chemistry, molecular modelling, metabolism, studies on the reactivity and biological functions of metabolites or effector molecules and their impact on cellular function. The team is organized into 4 interconnected thematic groups with shared technical support staff members.
Research Groups
MPN
Metabolism, Pharmacochemistry and Neurochemistry
BRed
Biochemistry Redox
IBRID
Immunology and Biochemistry for Rare Inflammatory Diseases
TBC
Targeting & Bioorthogonal Chemistry
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MPN (Metabolism, Pharmacochemistry and Neurochemistry)
The team MPN team is a multidisciplinary team composed of chemists and biochemists . Our current research projects are the following :
1. TRP metabolism (PIs: M-A Sari and J Dairou)
This is a joint project that will benefit from the expertise of the participants in the fields of P450 and the metabolism of endogenous and exogenous compounds, the P450-AhR relations ship and the regulation of CNS receptors such as mGluRs; It concerns the nature and biological activities of the metabolites formed from the compounds of the Kynurenine Pathway. This new research project of the new group indicated above will be developed in the 2019-2024 period. Very preliminary experiments have been started quite recently. This new project will benefit from the expertise of the participants in the fields of cytochromes P450 and the metabolism of endogenous and exogenous compounds, the P450-AhR relationships, and the regulation of various central nervous system (CNS) receptors such as the mGluR receptors. It concerns the “Nature and Biological Activities of the Metabolites Possibly Formed from the Compounds of the Kynurenine Pathway”. An increasing number of data have been published during these last few years to show that several metabolites issued from the catabolism of tryptophan (the “kynurenine” pathway) exhibit remarkable activities towards various receptors involved in the CNS and the immune system. This is true for kynurenine, xanthurenic acid, kynurenic acid, and cinnabarinic acid. Thus, this last compound was recently found as a good ligand of AhR and of several subtype4 mGluRs. However, the possible metabolism of these kynurenine derivatives by the P450-dependent monooxygenases has not been evaluated so far.
2. DJ-1-Park7 (PI J Dairou)
Recently, we showed that DJ-1/Park7, whose deficiency results in early onset parkinsonism, repairs guanines, both in the nucleotide pool and DNA, from their covalent contamination by glyoxals (R-CO-CHO), which are harmful by-products derived from glucose metabolism. The covalent addition of glyoxals to guanine is referred to as guanine glycation, and constitutes the major glycation assault to DNA. Unless repaired by DJ-1/Park7, the covalent reaction between glyoxals and guanine is responsible for mutations, DNA strand breaks and tumorigenesis. Moreover, like enzymes involved in guanine oxidation repair, DJ-1 may constitute a target for novel anti-cancer agents.
The study of the Parkinsonism-associated DJ-1/PARK7 will be continued and more precisely DJ-1 catalytic regulation by pesticides. Epidemiological studies also demonstrate a causal link between pesticides exposure and Parkinson’s disease. The aim of the project is the study of the effects of pesticides on DJ-1 activity in order to determine if DJ-1 is implicated in the link between pesticides and Parkinson’s disease. A second research axis concerns the identification of specific DJ-1/Park7 inhibitors that might function as novel anti-cancer agents (our discovery that DJ-1 is DNA and protein repair enzyme suggests that DJ-1 inhibitors could be anticancer agents). Increase of DJ-1 has been described in several types of cancers; however the mechanistic basis is still unclear. We suggest that increased DJ-1 expression may result from the increased aerobic glycolysis of cancer cells, necessary to meet the metabolic requirements of cell proliferation. In this context, we believed that DJ-1 could be a new target for anticancer drug development.
3. Medicinal Chemistry for the Modulation of Synaptic Transmission (PI Isabelle McCort)
The group is focused on small molecules that target receptors and transporters of synaptic transmission and their mechanisms. Using synthetic organic chemistry and molecular modeling, we develop pharmacological and therapeutic tools and investigate receptor activation and neurotransmitter transport. The team is involved in various projects from the initial design (molecules, 3D models…) all along to the in vivo studies.
Permanent researchers
Support staff
Post docs and PhD students
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Biochemistry Redox
In biology, redox-based signals regulate critical biological functions to suit the homeostatic metabolic balance and participate in both our health and the initiation and/or progression of many diseases, The redox effector toolkit includes the redox transition metals, reactive oxygen species (ROS) derived from dioxygen, reactive nitrogen species (RNS) derived from nitric oxide, and reactive sulfur species (RSS) derived from hydrogen sulfide (H2S).
In this general context, our team uses complementary skills in biochemistry, inorganic and organic syntheses and physical chemistry, as well as various spectroscopies, to tackle three main research axes:
We are interested in the synthesis and reactivity studies of biologically relevant sulfur-derivatives, with a strong focus on organic persulfides or inorganic complexes with disulfanido ligands.
We use reliable (bio)chemical tools to decipher their mechanisms of action on relevant model compounds and biological targets, and we apply an integrated approach to decode their biosynthesis as well as their implication under normal and inflammatory conditions.
We design and synthesize new probes for redox species or H2S, and develop their application both in vitro and in vivo.
Permanent researchers
Support staff
Post docs and PhD students
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Immunology and Biochemistry for Rare Inflammatory Diseases (IBRID)
Scientific projects and goals:
- Research Projects
Pathophysiology of juvenile dermatomyositis.
Juvenile dermatomyositis is a rare auto immune disease of unknown origin characterized by sustained overproduction of type I interferons. We are more specifically interested in the mechanisms responsible for this type I interferon overproduction/signature, and its impact on disease progression and severity. In line with this questioning, we are involved in clinical trials evaluating the benefit of inhibitors of interferon signalling in these patients.
Genotype / phenotype association in genetic auto-inflammatory diseases.
Numerous genes have been associated with inflammatory diseases. Interestingly, mutations in distinct domains of a same protein can be associated with distinct diseases, or variable manifestation of a same disease. We are interested in the molecular and cellular alterations resulting from mutations in different domains of a same protein, and its association with clinical features.
Pathophysiology of adult idiopathic inflammatory and autoimmune diseases.
The pathophysiology of most non-genetic inflammatory and autoimmune diseases is still poorly understood. We aim to identify deregulations of specific pathways within professional immune cells in patients suffering from idiopathic inflammatory or autoimmune diseases. This work should provide new insights into the mechanisms leading to the onset of the diseases and help identify new therapeutic targets or markers that predict the response to treatments
Main collaborators:
Dr Brigitte Bader Meunier – Necker Hospital
Dr Benjamin Chaigne – Cochin Hospital
Dr Julien Dairou – UMR8601
Dr Darragh Duffy – Pasteur Institut
Pr Sophie Georgin-Lavialle – Tenon Hospital
Dr. Marc Jansen – UMC Utrecht
Dr Laurent Le Corre – UMR8601
Dr Nicolas Michalski – Institut de L’audition / Pasteur Institut
Pr Pierre Quartier – Necker Hospital
Pr Angèle Soria – Tenon Hospital
Main Publications
Bader-Meunier B et al: Myositis specific autoantibody subtypes are associated with response to Janus kinase inhibitors in patients with juvenile dermatomyositis. Rheumatology. 2025
Maillet F*, Schmidt C*, et al: Increased mortality in diffuse systemic sclerosis patients with high circulating IFNα levels. J Invest Derm. 2024
Fayand A*, Cescato M* et al:Pathogenic variants in the NLRP3 LRR domain at position 861 are responsible for a boost-dependent atypical CAPS phenotype. J Allergy Clin Immunol. 2023
Fayand A, et al: Successful treatment of JAK1 associated inflammatory disease. J Allergy Clin Immunol. 2023
Le Voyer T et al, JAK inhibitors are effective in a subset of patients with juvenile dermatomyositis: a monocentric retrospective study. Rheumatology 2021.
Permanent researchers
Support staff
Post docs and PhD students
© all rights reserved
Targeting and Bioorthogonal Chemistry
The group’s research is centered around research themes at the interface of organic chemistry, chemical biology, and nanomedicine, offering a unique integration of approaches to develop new modular methods for generating biologically interesting entities. While direct impacts are expected in fields such as immunotherapy or synthetic biomaterials, the group’s ambition is to prepare diagnostic, therapeutic, and research tools that are broadly useful to the scientific community. The versatility of the processes developed paves the way for a multitude of applications with implications extending beyond the aforementioned research areas.
Main collaborators:
Pr. Yohann Corvis
Dr Nathalie Mignet
Dr Pierre Guermonprez
Permanent researchers
Support staff
Post docs and PhD students
Publications of the team
Journal articles
2024
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- Margaux Cescato, Laurence Cuisset, Laurent Le Corre, Mathieu Rodero, Sophie Georgin-Lavialle. Diagnosis traps for patients with acquired NLRP3 mutation. European Journal of Internal Medicine, 2024, 125 (16), pp.129-131. ⟨10.1016/j.ejim.2024.01.028⟩. ⟨hal-05073743⟩
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- Margaux Cescato, Yixiang y J Zhu, Laurent Le Corre, Bénédicte F Py, Sophie Georgin-Lavialle, et al.. Implication of the LRR Domain in the Regulation and Activation of the NLRP3 Inflammasome. Cells, 2024, 13 (16), pp.1365. ⟨10.3390/cells13161365⟩. ⟨hal-04695751⟩
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2023
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- Dylan Coelho, Laurent Le Corre, Karolina Bartosik, Laura Iannazzo, Emmanuelle Braud, et al.. Synthesis of Bisubstrate Analogues for RNA Methylation Studies using two Transition‐Metal‐Catalyzed Reactions. Chemistry - A European Journal, 2023, 29 (44), ⟨10.1002/chem.202301134⟩. ⟨hal-04246592⟩
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- ref_biblio
- Antoine Fayand, Véronique Hentgen, Céline Posseme, Carole Lacout, Capucine Picard, et al.. Successful treatment of JAK1 associated inflammatory disease. Journal of Allergy and Clinical Immunology, 2023, 152 (4), pp.972-983. ⟨10.1016/j.jaci.2023.06.004⟩. ⟨hal-04137977⟩
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- ref_biblio
- Antoine Fayand, Margaux Cescato, Laurent Le Corre, Alexandre Terré, Margaux Wacheux, et al.. Pathogenic variants in the NLRP3 LRR domain at position 861 are responsible for a boost-dependent atypical CAPS phenotype.. Journal of Allergy and Clinical Immunology, 2023, 152 (5), pp.1303-1311.e1. ⟨10.1016/j.jaci.2023.07.006⟩. ⟨hal-04182567⟩
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- ref_biblio
- Erwan Galardon, Nicolas Mathas, Dominique Padovani, Laurent Le Corre, Gabrielle Poncet, et al.. Persulfidation of DJ-1: Mechanism and Consequences. Biomolecules, 2023, 13 (1), pp.27. ⟨10.3390/biom13010027⟩. ⟨hal-03920432⟩
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- Laurent Le Corre, Dominique Padovani. Mechanism-based and computational modeling of hydrogen sulfide biogenesis inhibition: interfacial inhibition. Scientific Reports, 2023, 13 (1), pp.7287. ⟨10.1038/s41598-023-34405-3⟩. ⟨hal-04285208⟩
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- Afaf Mikou. Science et Société, une relation en pleine mutation. La Lettre de l'OCIM (Office de Coopération et d'Information Muséographique) : Musées, Patrimoine et Culture scientifiques et techniques, 2023, Médiation des sciences - L'expertise en dialogues (206), pp.62-73. ⟨hal-04227135⟩
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2022
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- Khawla Nouri, Nicolas Pietrancosta, Laurent Le Corre, Patrick Dansette, Daniel Mansuy, et al.. Human Orphan Cytochrome P450 2U1 Catalyzes the ω-Hydroxylation of Leukotriene B4. International Journal of Molecular Sciences, 2022, 23 (23), pp.14615. ⟨10.3390/ijms232314615⟩. ⟨hal-03957648⟩
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- ref_biblio
- Martin Oliver, Laurent Le Corre, Mélanie Poinsot, Michaël Bosco, Hongwei Wan, et al.. A Sub-Micromolar MraYAA Inhibitor with an Aminoribosyl Uridine Structure and a (S,S)-Tartaric Diamide: Synthesis, Biological Evaluation and Molecular Modeling. Molecules, 2022, 27 (6), pp.1769. ⟨10.3390/molecules27061769⟩. ⟨hal-03632451⟩
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- Hongwei Wan, Raja Ben Othman, Laurent Le Corre, Mélanie Poinsot, Martin Oliver, et al.. New MraYAA Inhibitors with an Aminoribosyl Uridine Structure and an Oxadiazole. Antibiotics, 2022, 11 (9), pp.1189. ⟨10.3390/antibiotics11091189⟩. ⟨hal-03805942⟩
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2021
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- Martin Oliver, Laurent Le Corre, Mélanie Poinsot, Alessandra Corio, Léa Madegard, et al.. Synthesis, biological evaluation and molecular modeling of urea-containing MraY inhibitors. Organic & Biomolecular Chemistry, 2021, 19 (26), pp.5844-5866. ⟨10.1039/D1OB00710F⟩. ⟨hal-03432617⟩
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- ref_biblio
- Claire Pujol, Anne Legrand, Livia Parodi, Priscilla Thomas, Fanny Mochel, et al.. Implication of folate deficiency in CYP2U1 loss of function. Journal of Experimental Medicine, 2021, 218 (11), pp.e20210846. ⟨10.1084/jem.20210846⟩. ⟨pasteur-03349041⟩
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- ref_biblio
- Tongtong Zhang, Laurent Le Corre, Olivia Reinaud, Benoit Colasson. A Promising Approach for Controlling the Second Coordination Sphere of Biomimetic Metal Complexes: Encapsulation in a Dynamic Hydrogen‐Bonded Capsule. Chemistry - A European Journal, 2021, 27 (1), pp.434-443. ⟨10.1002/chem.202004370⟩. ⟨hal-03154347⟩
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2020
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- Jeanne Fichez, Cathia Soulié, Laurent Le Corre, Sophie Sayon, Stéphane Priet, et al.. Discovery, SAR study and ADME properties of methyl 4-amino-3-cyano-1-(2-benzyloxyphenyl)-1 H -pyrazole-5-carboxylate as an HIV-1 replication inhibitor. RSC Medicinal Chemistry, 2020, 11 (5), pp.577-582. ⟨10.1039/D0MD00025F⟩. ⟨hal-03030936⟩
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- ref_biblio
- Afaf Mikou, Alexandre Cabayé, Anne Goupil, Hugues-Olivier Bertrand, Jean-Pierre Mothet, et al.. Asc-1 Transporter (SLC7A10): Homology Models And Molecular Dynamics Insights Into The First Steps Of The Transport Mechanism. Scientific Reports, 2020, 10, ⟨10.1038/s41598-020-60617-y⟩. ⟨hal-02996540⟩
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2019
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- Usama Ashraf, Laura Tengo, Laurent Le Corre, Guillaume Fournier, Patricia Busca, et al.. Destabilization of the human RED–SMU1 splicing complex as a basis for host-directed antiinfluenza strategy. Proceedings of the National Academy of Sciences of the United States of America, 2019, 116 (22), pp.10968-10977. ⟨10.1073/pnas.1901214116⟩. ⟨hal-02160991⟩
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2018
- ref_biblio
- Cécile Morlot, Daniel Straume, Katharina Peters, Olav A Hegnar, Nolwenn Simon, et al.. Structure of the essential peptidoglycan amidotransferase MurT/GatD complex from Streptococcus pneumoniae. Nature Communications, 2018, 9, pp.3180. ⟨10.1038/s41467-018-05602-w⟩. ⟨hal-01861372⟩
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2015
- ref_biblio
- Mickaël J Fer, Ahmed Bouhss, Mariana Patrão, Laurent Le Corre, Nicolas Pietrancosta, et al.. 5'-Methylene-triazole-substituted-aminoribosyl uridines as MraY inhibitors: synthesis, biological evaluation and molecular modeling.. Organic & Biomolecular Chemistry, 2015, 13 (26), pp.7193-222. ⟨10.1039/c5ob00707k⟩. ⟨hal-01433063⟩
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2012
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- Aurelie Jonquoy, Emilie Mugniery, Catherine Benoist-Lasselin, Nabil Kaci, Laurent Le Corre, et al.. A novel tyrosine kinase inhibitor restores chondrocyte differentiation and promotes bone growth in a gain-of-function Fgfr3 mouse model. Human Molecular Genetics, 2012, 21 (4), pp.841-851. ⟨10.1093/hmg/ddr514⟩. ⟨hal-01019795⟩
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2004
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- Virginie Binet, Carole Brajon, Laurent Le Corre, Francine Acher, Jean-Philippe Pin, et al.. The heptahelical domain of GABA(B2) is activated directly by CGP7930, a positive allosteric modulator of the GABA(B) receptor.. Journal of Biological Chemistry, 2004, 279 (28), pp.29085-91. ⟨10.1074/jbc.M400930200⟩. ⟨inserm-00318926⟩
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Conference papers
2021
- ref_biblio
- Afaf Mikou. Médiation scientifique : une facette du métier des chercheur.e.s ?. Science & You 2021, Université de Lorraine, Nov 2021, Metz, France. ⟨hal-03836950⟩
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- ref_biblio
- Afaf Mikou. Raising scientific awareness for better quality of life. ACS International Conference Pacifichem 2021 / Symposium session − Chemistry Education and Communication, American Chemical Society, Dec 2021, Honolulu, United States. ⟨hal-03747860⟩
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- ref_biblio
- Afaf Mikou, Alexandre Cabayé, Anne Goupil, Hugues-Olivier Bertrand, Jean-Pierre Mothet, et al.. Computational Study of the Asc−1 Transporter (SLC7A10): Insights Into The First Steps Of The Transport Mechanism. ACS International Conference Pacifichem 2021 / Symposium session − Crossing the Biological Membrane : Frontiers in the Computational Study of Membrane Transport., American Chemical Society, Dec 2021, Honolulu, United States. ⟨hal-03747858⟩
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Other publications
2023
- ref_biblio
- Afaf Mikou. Schizophrénie : une nouvelle cible thérapeutique pour certains symptômes méconnus. 2023. ⟨hal-04298700⟩
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Journal articles
2023
- ref_biblio
- Erwan Galardon, Nicolas Mathas, Dominique Padovani, Laurent Le Corre, Gabrielle Poncet, et al.. Persulfidation of DJ-1: Mechanism and Consequences. Biomolecules, 2023, 13 (1), pp.27. ⟨10.3390/biom13010027⟩. ⟨hal-03920432⟩
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2022
- ref_biblio
- Dominique Padovani, Erwan Galardon. Molecular Basis for the Interaction of Catalase with d -Penicillamine: Rationalization of Some of Its Deleterious Effects. Chemical Research in Toxicology, 2022, 35 (3), pp.412-421. ⟨10.1021/acs.chemrestox.1c00313⟩. ⟨hal-03646392⟩
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2016
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- Dominique Padovani, Assia Hessani, Francine T. Castillo, Géraldine Liot, Mireille Andriamihaja, et al.. Sulfheme formation during homocysteine S-oxygenation by catalase in cancers and neurodegenerative diseases. Nature Communications, 2016, 7, pp.1-13. ⟨10.1038/ncomms13386⟩. ⟨hal-01488442⟩
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2005
- ref_biblio
- Serge Gambarelli, Florence Luttringer, Dominique Padovani, Etienne Mulliez, Marc Fontecave. Activation of the anaerobic ribonucleotide reductase by S-adenosylmethionine.. ChemBioChem, 2005, 6 (11), pp.1960-1962. ⟨hal-00379330⟩
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