Search

Your search keyword '"Sophie Vichier-Guerre"' showing total 14 results
Start Over Author "Sophie Vichier-Guerre" Publication Year Range Last 10 years
14 results on '"Sophie Vichier-Guerre"'

1. Dynamic microfluidic single-cell screening identifies pheno-tuning compounds to potentiate tuberculosis therapy

Author

Maxime Mistretta, Mena Cimino, Pascal Campagne, Stevenn Volant, Etienne Kornobis, Olivier Hebert, Christophe Rochais, Patrick Dallemagne, Cédric Lecoutey, Camille Tisnerat, Alban Lepailleur, Yann Ayotte, Steven R. LaPlante, Nicolas Gangneux, Monika Záhorszká, Jana Korduláková, Sophie Vichier-Guerre, Frédéric Bonhomme, Laura Pokorny, Marvin Albert, Jean-Yves Tinevez, and Giulia Manina

Subjects
Science
Abstract

Abstract Drug-recalcitrant infections are a leading global-health concern. Bacterial cells benefit from phenotypic variation, which can suggest effective antimicrobial strategies. However, probing phenotypic variation entails spatiotemporal analysis of individual cells that is technically challenging, and hard to integrate into drug discovery. In this work, we develop a multi-condition microfluidic platform suitable for imaging two-dimensional growth of bacterial cells during transitions between separate environmental conditions. With this platform, we implement a dynamic single-cell screening for pheno-tuning compounds, which induce a phenotypic change and decrease cell-to-cell variation, aiming to undermine the entire bacterial population and make it more vulnerable to other drugs. We apply this strategy to mycobacteria, as tuberculosis poses a major public-health threat. Our lead compound impairs Mycobacterium tuberculosis via a peculiar mode of action and enhances other anti-tubercular drugs. This work proves that harnessing phenotypic variation represents a successful approach to tackle pathogens that are increasingly difficult to treat.

Published
2024
Full Text
View/download PDF

2. Structural analysis of the Trypanosoma brucei EIF4E6/EIF4G5 complex reveals details of the interaction between unusual eIF4F subunits

Author

Renato Ferras Penteado, Renata Santana da Silva, Danielle Maria Nascimento Moura, Gustavo Barbosa de Lima, Amaranta Muniz Malvezzi, Tallyta Tâmara da Silva Monteiro, Camila Cavalcanti Xavier, Sophie Vichier-Guerre, Laurence Dugué, Sylvie Pochet, Nilson Ivo Tonin Zanchin, Christian Robson de Souza Reis, Osvaldo Pompílio de Melo Neto, and Beatriz Gomes Guimarães

Subjects
Medicine, Science
Abstract

Abstract Recognition of the mRNA 5′ end is a critical step needed for translation initiation. This step is performed by the cap binding protein eIF4E, which joins the larger eIF4G subunit to form the eIF4F complex. Trypanosomatids have a minimum of five different eIF4F-like complexes formed through specific but not well-defined interactions between four different eIF4E and five eIF4G homologues. The EIF4E6/EIF4G5 complex has been linked with the stage-specific translation of mRNAs encoding the major Trypanosoma brucei virulence factors. Here, to better define the molecular basis for the TbEIF4E6/TbEIF4G5 interaction, we describe the identification of the peptide interacting with TbEIF4E6 in the region comprising residues 79–166 of TbEIF4G5. The TbEIF4E6-TbEIF4G5_79-116 complex reconstituted with recombinant proteins is highly stable even in the absence of cap-4. The crystal structure of the complex was subsequently solved, revealing extensive interacting surfaces. Comparative analyses highlight the conservation of the overall structural arrangement of different eIF4E/eIF4G complexes. However, highly different interacting surfaces are formed with distinct binding contacts occurring both in the canonical and noncanonical elements within eIF4G and the respective eIF4E counterpart. These specific pairs of complementary interacting surfaces are likely responsible for the selective association needed for the formation of distinct eIF4F complexes in trypanosomatids.

Published
2024
Full Text
View/download PDF

3. Dynamic microfluidic single-cell screening identifies pheno-tuning compounds to potentiate tuberculosis therapy

Author

Maxime Mistretta, Mena Cimino, Pascal Campagne, Stevenn Volant, Etienne Kornobis, Olivier Hebert, Christophe Rochais, Patrick Dallemagne, Cédric Lecoutey, Camille Tisnerat, Alban Lepailleur, Yann Ayotte, Steven R. LaPlante, Nicolas Gangneux, Monika Záhorszká, Jana Korduláková, Sophie Vichier-Guerre, Frédéric Bonhomme, Laura Pokorny, Marvin Albert, Jean-Yves Tinevez, and Giulia Manina

Abstract

Drug-recalcitrant infections are a leading global-health concern. Bacterial cells benefit from phenotypic variation, which can suggest effective anti-microbial strategies. However, probing phenotypic variation entails spatiotemporal analysis of individual cells that is technically challenging, and hard to integrate into drug discovery. To address this, we developed a flow-controlled multi-condition microfluidic platform suitable for imaging two-dimensional growth of bacterial cells, compressed inside separate microchambers by a soft hydro-pneumatic membrane. With this platform, we implemented a dynamic single-cell screening for compounds that induce a phenotypic change while decreasing cell-to-cell variation, aiming to undermine the bacterial population, making it more vulnerable to other drugs. We first applied this strategy to mycobacteria, as tuberculosis poses a major public-health threat. Our top hit impairsMycobacterium tuberculosisvia a peculiar mode of action and enhances other anti-tubercular drugs. This work proves that pheno-tuning compounds represent a successful approach to tackle pathogens that are increasingly difficult to treat.

Published
2023
Full Text
View/download PDF

4. Interaction network among de novo purine nucleotide biosynthesis enzymes in Escherichia coli

Author

Antoine Gedeon, Gouzel Karimova, Nour Ayoub, Julien Dairou, Quentin Giai Gianetto, Sophie Vichier‐Guerre, Pierre‐Olivier Vidalain, Daniel Ladant, Hélène Munier‐Lehmann, Chimie et Biocatalyse, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université Paris Cité (UPCité), Biochimie des Interactions Macromoléculaires / Biochemistry of Macromolecular Interactions, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Plateforme de Protéomique / Proteomics platform, Université Paris Cité (UPCité)-Spectrométrie de Masse pour la Biologie – Mass Spectrometry for Biology (UTechS MSBio), Institut Pasteur [Paris] (IP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut Pasteur [Paris] (IP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Spectrométrie de Masse pour la Biologie – Mass Spectrometry for Biology (UTechS MSBio), Institut Pasteur [Paris] (IP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Chimie biologique épigénétique - Epigenetic Chemical Biology (EpiCBio), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and This work was supported in part by the Centre National de la Recherche Scientifique (CNRS), the Institut National de la Santé Et de la Recherche Médicale (INSERM), and the Institut Pasteur.Antoine Gedeon and Nour Ayoub acknowledge PhD fellowships from the Médicament, Toxicologie, Chimieet Imageries PhD school (MTCI, ED 563), Université Paris Cité.

Subjects
bacterial two-hybrid system, [SDV]Life Sciences [q-bio], Escherichia coli, Cell Biology, de novo purine biosynthesis, Molecular Biology, Biochemistry, supramolecular assembly
Abstract

International audience; In human cells, de novo purine nucleotide biosynthesis is known to be regulated through the formation of a metabolon called purinosome. Here, we employed a bacterial two-hybrid approach to characterize the protein-protein interactions network among the corresponding enzymes of Escherichia coli. Our study revealed a dense network of binary interactions that connect most purine nucleotide biosynthesis enzymes. Notably, PurK, an exclusive prokaryotic enzyme, appears as one of the central hubs of this network. We further showed that modifications in PurK, which disrupted several interactions in the network, affected the purine nucleotide pools and altered the bacterial fitness. Our data suggest that the bacterial de novo purine nucleotide biosynthesis enzymes can assemble in a supramolecular complex and that proper interactions among the components of this complex can contribute to bacterial fitness.

Published
2023
Full Text
View/download PDF

6. Identification of Chemical Probes Targeting MBD2

Author

Diane Erdmann, Jean Contreras, Rémy A. Le Meur, Bruno Vitorge, Vincent Saverat, Ambre Tafit, Corinne Jallet, Véronique Cadet-Daniel, Corentin Bon, Phannarath Phansavath, Virginie Ratovelomanana-Vidal, Albert Jeltsch, Sophie Vichier-Guerre, J. Iñaki Guijarro, Paola B. Arimondo, Chimie biologique épigénétique - Epigenetic Chemical Biology (EpiCBio), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Plateforme Technologique de RMN Biologique et HDX-MS - Biological NMR and HDX-MS Technological Platform, Institute of Chemistry for Life and Health Sciences (iCLeHS), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), University of Stuttgart, The 800-MHz NMR spectrometer of the Institut Pasteur was partially funded by the Région Ile de France (SESAME 2014 NMRCHR grant no. 4014526). The project was financed by the French PPR Antiobioresistance ANR-20-PAMR-0011–TheraEPI (to P.B.A.)., We thank Prof. Srinivasan and Prof. Nelson from the Sidney Kimmel Comprehensive Cancer Center at the University of Medicine, Johns Hopkins (Baltimore, MD) for the kind gift of MBD2-His plasmid. We thank Ludovic Halby for the design of the synthetic pathway and for the fruitful discussions on the project conception., and ANR-20-PAMR-0011,TherAEPI,Thérapies épigénétiques pour esquiver la résistance(2020)

Subjects
DNA-Binding Proteins, 5-Methylcytosine, Humans, Molecular Medicine, CpG Islands, DNA, General Medicine, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, DNA Methylation, Biochemistry
Abstract

International audience; Epigenetics has received much attention in the past decade. Many insights on epigenetic (dys)regulation in diseases have been obtained, and clinical therapies targeting them are in place. However, the readers of the epigenetic marks are lacking enlightenment behind this revolution, and it is poorly understood how DNA methylation is being read and translated to chromatin function and cellular responses. Chemical probes targeting the methyl-CpG readers, such as the methyl-CpG binding domain proteins (MBDs), could be used to study this mechanism. We have designed analogues of 5-methylcytosine to probe the MBD domain of human MBD2. By setting up a protein thermal shift assay and an AlphaScreen-based test, we were able to identify three fragments that bind MBD2 alone and disrupt the MBD2-methylated DNA interactions. Two-dimensional NMR experiments and virtual docking gave valuable insights into the interaction of the ligands with the protein showing that the compounds interact with residues that are important for DNA recognition. These constitute the starting point for the design of potent chemical probes for MBD proteins.

Published
2022
Full Text
View/download PDF

7. Crystal structure of the Trypanosoma cruzi EIF4E5 translation factor homologue in complex with mRNA cap-4

Author

Bruno Moisés de Matos, Sophie Vichier-Guerre, Tatiana Reichert da Silva Assunção, Laurence Dugué, Nilson Ivo Tonin Zanchin, Beatriz G. Guimarães, Sylvie Pochet, Lidia Watanabe Reolon, Fiocruz Paraná - Instituto Carlos Chagas / Carlos Chagas Institute [Curitiba, Brésil] (ICC), Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Instituto Federal Paraná (IFPR), Chimie et Biocatalyse, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Fundação Araucária [05/2016], Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES Financing code 001), Conselho Nacional de Desenvolvimento Científico e Tecnológico [CNPq, NITZ 312195/2015-0 BGG 304027/2015-4 and LWR fellowship], Fundação Oswaldo Cruz. The authors also acknowledge financial support from Institut Pasteur and Centre National de la Recherche Scientifique (CNRS). Funding for open access charge: Fundação Oswaldo Cruz., The authors acknowledge the Platform for Protein Purification and Characterization of the FIOCRUZ Technical Platform program. The authors are grateful to Synchrotron SOLEIL for beam time awarded at PROXIMA1 and PROXIMA2a beam lines (Proposal 20160778) and all the support they benefited as SOLEIL’s users. We thank Jean-Sebastien Vartanian-Grimaldi for technical help during the preparation of ACSS. Yves L. Janin is also acknowledged for his help in proof-reading this manuscript. Electrostatic potential analyses were performed with UCSF Chimera, developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco, with support from NIH P41-GM103311, Fundação Oswaldo Cruz (FIOCRUZ), and Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]

Subjects
Models, Molecular, RNA Caps, Trypanosoma, Stereochemistry, Trypanosoma cruzi, Oligonucleotides, RNA-binding protein, Biology, Crystallography, X-Ray, Ligands, RNA Cap Analogs, 03 medical and health sciences, 0302 clinical medicine, Structural Biology, Genetics, [CHIM]Chemical Sciences, Animals, Humans, Initiation factor, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, RNA, Messenger, Translation factor, 030304 developmental biology, 0303 health sciences, Messenger RNA, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], [CHIM.ORGA]Chemical Sciences/Organic chemistry, Nucleotides, Oligonucleotide, EIF4E, Temperature, RNA, Translation (biology), Schistosoma mansoni, DNA Methylation, Eukaryotic Initiation Factor-4E, Carrier Proteins, 030217 neurology & neurosurgery, Protein Binding
Abstract

International audience; Association of the initiation factor eIF4E with the mRNA cap structure is a key step for translation. Trypanosomatids present six eIF4E homologues, showing a low conservation and also differing significantly from the IF4Es of multicellular eukaryotes. On the mRNA side, while in most eukaryotes the mRNA contains cap-0 (7-methyl-GTP), the trypanosomatid mRNA features a cap-4, which is formed by a cap-0, followed by the AACU sequence containing 2'-O-ribose methylations and base methylations on nucleotides 1 and 4. The studies on eIF4E-cap-4 interaction have been hindered by the difficulty to synthesize this rather elaborated cap-4 sequence. To overcome this problem, we applied a liquid-phase oligonucleotide synthesis strategy and describe for the first time the crystal structure of a trypanosomatid eIF4E (T. cruzi EIF4E5) in complex with cap-4. The TcEIF4E5-cap-4 structure allowed a detailed description of the binding mechanism, revealing the interaction mode for the AACU sequence, with the bases packed in a parallel stacking conformation and involved, together with the methyl groups, in hydrophobic contacts with the protein. This binding mechanism evidences a distinct cap interaction mode in comparison with previously described eIF4E structures and may account for the difference of TcEIF4E5-cap-4 dissociation constant in comparison with other eIF4E homologues.

Published
2019
Full Text
View/download PDF

8. An Expedient Synthesis of Flexible Nucleosides through Enzymatic Glycosylation of Proximal and Distal Fleximer Bases

Author

Katherine L. Seley-Radtke, Therese Ku, Sophie Vichier-Guerre, Sylvie Pochet, Chimie et Biocatalyse, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], University of Maryland [Baltimore County] (UMBC), University of Maryland System, National Institute of Allergy and Infectious Diseases. Grant Number: R21 AI118470-01National Institute of General Medical Sciences. Grant Number: T32 GM066706Institut PasteurCentre National de la Recherche Scientifique, and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Glycosylation, biocatalysis, Purine nucleoside phosphorylase, 010402 general chemistry, medicine.disease_cause, fleximers, 01 natural sciences, Biochemistry, Surname(s) of Author(s) including Corresponding Author(s), Nucleobase, chemistry.chemical_compound, Very Important Paper, Lactobacillus leichmannii, Ribose, medicine, Escherichia coli, Pentosyltransferases, Initial(s), Molecular Biology, itle(s), Molecular Structure, 010405 organic chemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Communication, Organic Chemistry, deoxyribosyltransferase, Communications, purine nucleoside phosphorylase, 0104 chemical sciences, chemistry, Purine-Nucleoside Phosphorylase, Biocatalysis, Molecular Medicine, Nucleoside, Function (biology), nucleosides
Abstract

The structurally unique “fleximer” nucleosides were originally designed to investigate how flexibility in a nucleobase could potentially affect receptor–ligand recognition and function. Recently they have been shown to have low‐to‐sub‐micromolar levels of activity against a number of viruses, including coronaviruses, filoviruses, and flaviviruses. However, the synthesis of distal fleximers in particular has thus far been quite tedious and low yielding. As a potential solution to this issue, a series of proximal fleximer bases (flex‐bases) has been successfully coupled to both ribose and 2′‐deoxyribose sugars by using the N‐deoxyribosyltransferase II of Lactobacillus leichmannii (LlNDT) and Escherichia coli purine nucleoside phosphorylase (PNP). To explore the range of this facile approach, transglycosylation experiments on a thieno‐expanded tricyclic heterocyclic base, as well as several distal and proximal flex‐bases were performed to determine whether the corresponding fleximer nucleosides could be obtained in this fashion, thus potentially significantly shortening the route to these biologically significant compounds. The results of those studies are reported herein., A thieno‐expanded tricyclic base and several distal and proximal flex‐bases have been converted into their corresponding fleximer nucleosides by enzymatic transglycosylation reactions catalyzed by N‐deoxyribosyltransferase from L. leichmannii (LlNDT) or E. coli purine nucleoside phosphorylase (PNP).

Published
2020
Full Text
View/download PDF

9. First-in-class allosteric inhibitors of bacterial IMPDHs

Author

Gilles Labesse, Olivier Helynck, Sophie Vichier-Guerre, Thomas Alexandre, Muriel Gelin, Hélène Munier-Lehmann, Alexandru Lupan, Laurence Dugué, Ahmed Haouz, Université Sorbonne Paris Cité (USPC), Chimie et Biocatalyse, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre de Biochimie Structurale [Montpellier] (CBS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Cristallographie (Plateforme) - Crystallography (Platform), This work was supported in part by the Centre National de la Recherche Scientifique (CNRS), the Institut National de la Santé Et de la Recherche Médicale (INSERM), the Institut Pasteur, the Conseil Régional d'Ile-de-France (Chemical Library Project, grants n° I 06-222/R and I 09-1739/R, which included a postdoctoral fellowship for Alexandru Lupan) and the French Infrastructure for Integrated Structural Biology (FRISBI) ANR-10-INBS-05.Thomas Alexandre was a recipient of a PhD fellowship from the Conseil Régional d'Ile-de-France and the 'D.I.M. maladies infectieuses, parasitaires et nosocomiales émergentes' 2011., We thank Emilie Dufour for participation in the chemical library screening, Zakaria Jemouai for participation in the kinetic characterization of the allosteric inhibitors and Aurélie Bourderioux for performing the fluorescence experiments. We thank the Molecular Biophysics facility (PFBMI, Institut Pasteur, Paris) for their technical assistance and helpful suggestions. The authors are grateful to the staff of the Crystallographic platform from the Institut Pasteur for robot-driven crystallization screening. We thank Alexandre Chenal for fruitful discussion and technical assistance for fluorescence experiments, and Thomas J. Dougherty for careful reading of this manuscript. We acknowledge the Synchrotron SOLEIL (St Aubin, France) staff for assistance and advice during data collection on PROXIMA-1 (X-ray diffraction data) and SWING (SAXS data) beamlines., ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010), Munier-Lehmann, Hélène, Infrastructure Française pour la Biologie Structurale Intégrée - - FRISBI2010 - ANR-10-INBS-0005 - INBS - VALID, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], and Cristallographie (Plate-forme)

Subjects
MESH: IMP Dehydrogenase, Drug target, Dehydrogenase, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 01 natural sciences, Nucleotide metabolism, MESH: Allosteric Regulation, IMPDH, MESH: Apoproteins, Low affinity, Adenosine Triphosphate, IMP Dehydrogenase, Drug Discovery, MESH: Adenosine Triphosphate, Enzyme Inhibitors, MESH: Bacterial Proteins, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, 0303 health sciences, Effector, [CHIM.ORGA]Chemical Sciences/Organic chemistry, General Medicine, Bateman domain, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Biochemistry, MESH: Enzyme Inhibitors, MESH: Protein Domains, Allosteric inhibitor, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, Allosteric regulation, Chemical library screening, Small Molecule Libraries, 03 medical and health sciences, Allosteric Regulation, Bacterial Proteins, Protein Domains, Oxidoreductase, MESH: Small Molecule Libraries, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Quaternary structure, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Pharmacology, 010405 organic chemistry, Organic Chemistry, [CHIM.ORGA] Chemical Sciences/Organic chemistry, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 0104 chemical sciences, Enzyme, chemistry, Protein quaternary structure, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Apoproteins
Abstract

International audience; Inosine-5'-monophosphate dehydrogenase (IMPDH) is an essential enzyme in many bacterial pathogens and is considered as a potential drug target for the development of new antibacterial agents. Our recent work has revealed the crucial role of one of the two structural domains (i.e. Bateman domain) in the regulation of the quaternary structure and enzymatic activity of bacterial IMPDHs. Thus, we have screened chemical libraries to search for compounds targeting the Bateman domain and identified first in-class allosteric inhibitors of a bacterial IMPDH. These inhibitors were shown to counteract the activation by the natural positive effector, MgATP, and to block the enzyme in its apo conformation (low affinity for IMP). Our structural studies demonstrate the versatility of the Bateman domain to accommodate totally unrelated chemical scaffolds and pave the way for the development of allosteric inhibitors, an avenue little explored until now.

Published
2019
Full Text
View/download PDF

10. An expedient synthesis of flexible nucleosides via a regiocontrolled enzymatic glycosylation of functionalized imidazoles

Author

Laurence Dugué, Sylvie Pochet, Frédéric J. Bonhomme, Sophie Vichier-Guerre, Chimie et Biocatalyse, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), The authors gratefully acknowledge financial support from the Institut Pasteur and CNRS., Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]

Subjects
Glycosylation, 010402 general chemistry, 01 natural sciences, Biochemistry, Catalysis, chemistry.chemical_compound, [CHIM]Chemical Sciences, Organic chemistry, Imidazole, Pentosyltransferases, Physical and Theoretical Chemistry, chemistry.chemical_classification, Reaction conditions, Molecular Structure, Aqueous medium, 010405 organic chemistry, Organic Chemistry, Imidazoles, Regioselectivity, Nucleosides, 0104 chemical sciences, Enzyme, chemistry, Nucleoside, DNA
Abstract

International audience; A versatile two-step synthesis of C4- and C5-arylated 2′-deoxyribosylimidazoles was elaborated using enzymatic N-transglycosylation followed by microwave-assisted Pd-catalysed arylation reactions. We report herein the reaction conditions that permit managing regioselectivity (N3 versus N1-isomers) in the enzymatic glycosylation of 4-iodoimidazole using the nucleoside N-deoxyribosyltransferase from L. leichmannii. Regiocontrolled glycosylation was also observed among several other imidazole derivatives studied, providing simple access to isomers not readily accessible by chemical routes. Finally, a series of flexible nucleosides was obtained in one step from 4- or 5-iodo-imidazole nucleosides by the Suzuki–Miyaura cross-coupling reaction with (hetero)aryl-boronic acids in aqueous media. Moreover, this chemoenzymatic approach is compatible with a one-pot two-step process affording a straightforward access to a broad array of potential anticancer and antiviral drugs as well as new DNA building blocks.

Published
2017
Full Text
View/download PDF

11. 2′-Deoxyribonucleoside 5′-triphosphates bearing 4-phenyl and 4-pyrimidinyl imidazoles as DNA polymerase substrates

Author

Laurence Dugué, Sophie Vichier-Guerre, Sylvie Pochet, Chimie Organique, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), The authors gratefully acknowledge financial support from the Institut Pasteur and the CNRS., and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
DNA polymerase, Stereochemistry, Deoxyribonucleosides, DNA-Directed DNA Polymerase, 010402 general chemistry, 01 natural sciences, Biochemistry, Polymerization, chemistry.chemical_compound, Polyphosphates, Animals, Imidazole, Nucleotide, Deoxynucleoside triphosphate, Physical and Theoretical Chemistry, chemistry.chemical_classification, Base Sequence, biology, 010405 organic chemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Organic Chemistry, Imidazoles, DNA Polymerase I, 0104 chemical sciences, Deoxyribonucleoside, Pyrimidines, chemistry, Terminal deoxynucleotidyl transferase, biology.protein, Cattle, Derivative (chemistry)
Abstract

International audience; We developed a versatile access to a series of 4-substituted imidazole 2'-deoxynucleoside triphosphate bearing functionalized phenyl or pyrimidinyl rings. 4-Iodo-1H-imidazole was enzymatically converted into the corresponding 2'-deoxynucleoside, which was then chemically derived into its 5'-triphosphate, followed by 4-arylation via Suzuki-Miyaura coupling using (hetero)arylboronic acids. Both KF (exo-) and Deep Vent (exo-) DNA polymerases incorporated these modified nucleotides in primer-extension assays, adenine being the preferred pairing partner in the template. The 4-(3-aminophenyl)imidazole derivative (3APh) was the most efficiently inserted opposite A by KF (exo-) with only a 37-fold lower efficiency (Vmax/KM) than that of the correct dTTP. No further extension occurred after the incorporation of a single aryl-imidazole nucleotide. Interestingly, the aryl-imidazole dNTPs were found to undergo successive incorporation by calf thymus terminal deoxynucleotidyl transferase with different tailing efficiencies among this series and with a marked preference for 2APyr polymerization.

Published
2019
Full Text
View/download PDF

12. Cover Feature: An Expedient Synthesis of Flexible Nucleosides through Enzymatic Glycosylation of Proximal and Distal Fleximer Bases (ChemBioChem 10/2020)

Author

Therese Ku, Sophie Vichier-Guerre, Sylvie Pochet, and Katherine L. Seley-Radtke

Subjects
chemistry.chemical_classification, Glycosylation, Organic Chemistry, Purine nucleoside phosphorylase, Biochemistry, chemistry.chemical_compound, Enzyme, chemistry, Biocatalysis, Feature (computer vision), Molecular Medicine, Cover (algebra), Molecular Biology
Published
2020
Full Text
View/download PDF

13. Expedient and generic synthesis of imidazole nucleosides by enzymatic transglycosylation

Author

Laurence Dugué, Sophie Vichier-Guerre, Sylvie Pochet, Frédéric J. Bonhomme, Chimie et Biocatalyse, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Glycosylation, Purine nucleoside phosphorylase, Nucleoside deoxyribosyltransferase, Pentosyltransferases/chemistry, 010402 general chemistry, 01 natural sciences, Biochemistry, Catalysis, chemistry.chemical_compound, Imidazole, Pentosyltransferases, Imidazoles/chemical synthesis, Physical and Theoretical Chemistry, Solubility, Chromatography, High Pressure Liquid, Chromatography, [CHIM.ORGA]Chemical Sciences/Organic chemistry, 010405 organic chemistry, Organic Chemistry, Imidazoles, Nucleosides, Combinatorial chemistry, 0104 chemical sciences, Nucleosides/chemical synthesis, chemistry, High Pressure Liquid, Molecular probe, Nucleoside
Abstract

International audience; A straightforward route to original imidazole-based nucleosides that makes use of an enzymatic N-transglycosylation step is reported in both the ribo- and deoxyribo-series. To illustrate the scope of this approach, a diverse set of 4-aryl and 4-heteroaryl-1H-imidazoles featuring variable sizes and hydrogen-bonding patterns was prepared using a microwave-assisted Suzuki-Miyaura cross-coupling reaction. These imidazole derivatives were examined as possible substrates for the nucleoside 2'-deoxyribosyltransferase from L. leichmannii and the purine nucleoside phosphorylase from E. coli. The optimum transglycosylation conditions, including the use of co-adjuvants to address solubility issues, were defined. Enzymatic conversion of 4-(hetero)arylimidazoles to 2'-deoxyribo- or ribo-nucleosides proceeded in good to high conversion yields, except bulky hydrophobic imidazole derivatives. Nucleoside deoxyribosyltransferase of class II was found to convert the widest range of functionalized imidazoles into 2'-deoxyribonucleosides and was even capable of bis-glycosylating certain heterocyclic substrates. Our findings should enable chemoenzymatic access to a large diversity of flexible nucleoside analogues as molecular probes, drug candidates and original building blocks for synthetic biology.

Published
2016
Full Text
View/download PDF

14. Direct Synthesis of Allyl Amines with 2‐Nitrosulfonamide Derivatives via the Tsuji‐Trost Reaction

Author

Bon, Corentin, Arimondo, Paola B, Halby, Ludovic, Chimie biologique épigénétique - Epigenetic Chemical Biology (EpiCBio), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), École Doctorale Bio Sorbonne Paris Cité [Paris] (ED BioSPC), Université Sorbonne Paris Cité (USPC)-Université de Paris (UP), Région Ile de France supported the research with a Ph.D. fellowship to CB (ARDoC), la Ligue contre le cancer, Comité de Paris, to PBA (RS20/75-82 and RS21/75-31)., We thank Bruno Vitorge from the Institut Pasteur Biological NMR Technological Platform for helping with NMR experiments, Frédéric Bonhomme of the CNRS-Institut Pasteur UMR3523 Organic Chemistry Unit for assisting with HRMS analysis. Sophie Vichier-Guerre of the CNRS-Institut Pasteur UMR3523 Organic Chemistry Unit for assisting with LC/MS analysis. The authors are thankful to Alain Guy and Clotilde Ferroud, CNAM, Paris, for their teaching on the use of the nosyl as protecting group., Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), École Doctorale Bio Sorbonne Paris Cité [Paris] (ED562 - BioSPC), and Université Sorbonne Paris Cité (USPC)-Université Paris Cité (UPCité)

Subjects
Chemistry, nosyl groups, Tsuji-Trost reactions, [SDV]Life Sciences [q-bio], Communication, conjugated allyl amines, allylation reactions, palladium, QD1-999, Communications
Abstract

The Tsuji‐Trost Reaction is a palladium‐catalysed allylation of nucleophiles that consists in the reaction of a nitrogen, carbon or oxygen‐based nucleophiles with an allylic substrate bearing a leaving group. Here we present the use of 2‐nitrosulfonamide derivatives as nucleophile, which are reactive under mild conditions. 2‐nitrosulfonyl groups are well‐known dual protective activator groups easy to introduce in any type of amine substrates. The resulting 2‐nitrosulfonamide derivatives are ideal substrates for the Tsuji‐Trost reaction to afford a convenient and flexible access to primary and dissymmetric secondary allyl amines. The optimised procedure is flexible (for solvent, temperature, functional groups) and has been applied with good to excellent yield to access to a wide range of allyl amine derivatives., A direct method for the allylation of 2‐nitrosulfonamides is described and exemplified. The mild and flexible conditions used as well as the ease to remove the 2‐nitrosulfonamide group are compatible with a large set of chemical moieties.

Published
2021
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results