Nuclear Magnetic Resonance Spectroscopy

From left to right: Xi Chen (PhD), Eugen Lin (Intern, Imperial College), Cedric Caradeuc, Gildas Bertho, Laura Prieur, Mathieu Baudin, Nicolas Giraud

Team Description

The research group on NMR of Biological Substances is part of the team Bio-Spectroscopies. We develop analytical methods based on Nuclear Magnetic Resonance that we apply to the study of biological systems of major interest. Our research activity covers a wide range of projects ranging from the study of the interaction of small molecules with proteins, to the metabolomic analysis of biological fluids.

We design novel experiments to exceed the sensitivity and resolution limits of traditional NMR analyzes on complex samples. We are also working on the development of modelling and data analysis tools to make the best use of the information obtained on the biological systems under study. 

These projects are carried out in the frame of several collaborations with  laboratories working in the fields of organic chemistry, biochemistry, structural biology or medical research.

 

Research Themes

Methodological developments for ultra-high resolution NMR

We develop original concepts which aim at enhancing resolution in spectra of complex samples, to a point where their analysis becomes a faster, easier, and a more accurate process. 

Since the advent of Fourier transform NMR, a vast number of pulse sequences have been specifically designed, that allow to probe a great number of spin interactions on 1D and 2D spectra. Unfortunately, in most of the systems that are of interest to the scientific community nowadays especially in the biomedical field, the size or the complexity of the molecular architecture which is probed often leads to overcrowded spectra whose resolution is too low to give access to their analytical content.

In this context, we develop new analytical tools based on « pure shift » and « J-edited » NMR methods, and to apply them to challenging chemical and/or biological systems. Some of our most recent developments are described below. 

Pure Shift NMR applied to metabolomics analysis of cancer cells (coll. V. Baud and C. Thieblemont)

We have recently developed a “pure shift” version of the 1H 1D NOESY-presat experiment used for metabolomics. We have successfully applied it to an extra cellular medium taken from a cancer cell line. We have shown that we can detect metabolites in cancer cells, with a significant improvement of their spectral resolution, within an experimental time that is compatible with standard analytical workflows. The analysis of the resulting pure shift data obtained for a series of 40 Diffuse Large B-Cell (DLBCL) exo-metabolomes shows that we can observe individually about 85 % of the 40 metabolites usually reported in literature for extra cellular media in cancer studies. Furthermore, the statistical analyses performed on the “pure shift” dataset show that they are suitable for a clean separation of the groups of cells undergoing different anti-metabolic treatments, despite their lower sensitivity.

A) Pure shift and standard 1H NMR spectra (500 MHz) of an extra cellular medium from a DLBCL cell line treated with a combination of anti-metabolic drugs. B) Regions highlighting the resolution achieved in pure shift data for a collection of 40 DLBCL samples. C) Statistical analyses performed on “standard” and “pure shift” datasets.

Monitoring Conformational Changes in an Enzyme Conversion Inhibitor Using Pure Shift EXSY

We have also achieved recently the acquisition of 2D NMR EXSY spectra with ultrahigh resolution, which allowed us for probing the slow conformational exchange process in a pharmaceutical compound.

The resolution enhancement is achieved by implementing interferogram based PSYCHE homonuclear decoupling to generate a pure shift proton spectrum along the direct domain of the resulting data.

We have shown that although being less sensitive and requiring a longer acquisition time, the quality of pure shift spectra allows for extracting exchange rates values that are coherent with the ones determined by standard approach, on a temperature range that demonstrates the robustness of the chosen homonuclear decoupling method.

The resolution enhancement provided by the simplification of proton lineshape allows for probing a higher number of proton sites whose analysis would have been biased using a standard method. These results open the way to a thorough and accurate study of chemical exchange processes based on a multi-site analysis of  2D pure shift EXSY spectra

Dynamic and structural study of biomolecular interactions

Over the last years, our group has brought several contributions to the field of biomolecular interactions analysis. We develop experimental and theoretical methods for probing both dynamic and structural features of the supramolecular interactions that are underlying several biological processes. 

Describing and understanding supramolecular interactions in large biological or bio-mimetic systems has become a major stake over the recent years. However, despite the considerable progress that have been achieved in this field, probing at an atomic scale protein-protein, protein-nucleic acid, protein-lipid, protein-carbohydrate interactions, or the interactions with small molecules, enzyme substrates and regulators, still constitutes a critical challenge for chemists and biochemists.

Deciphering supramolecular interactions between lanthanide complexes and proteins

We have carried out a fruitful collaboration with the groups of Dr. Olivier Maury and Pr. Elise Dumont at Ecole Normale Supérieure de Lyon to develop and understand the properties of Lanthanide derivatives that were shown to interact non-covalently with a broad range of proteins.

In this spirit, we had shown that some Tris(dipicolinate)-lanthanide complexes ([Ln(DPA)3]3- (DPA = dipicolinate = pyridine-2,6-dicarboxylate) interact strongly with specific amino-acids from the proteins, and thus can co-crystallize with them. This approach was demonstrated as a method of choice for incorporating a lanthanide derivative within the protein crystal, hereby exploiting their large anomalous signal for anomalous diffraction in crystallography, alongside with their well-known luminescence property. On the other hand, these lanthanide complexes have also been identified among the most promising non-covalent paramagnetic tags to probe the structure of proteins and peptides by NMR, both in solution and in the solid state. The analysis of the binding mode between [Ln(DPA)3]3- and model proteins has allowed us to evidence a supramolecular effect that mainly involves the tri-anionic complexes and cationic amino-acid residues. Notably, we had identified a preferential supramolecular interaction with arginine residues in protein systems over lysine and histidine, respectively.

Paramagnetic DOSY

Diffusion Ordered NMR SpectroscopY (DOSY) has been shown to be a method of choice for probing a wide range of molecular assemblies by measuring the rate at which they diffuse through the NMR sample, according to their size, or their interaction with their environment. We have implemented diffusion ordered NMR to determine accurately the mobility of paramagnetic tris-dipicolinate lanthanide complexes that are versatile probes of protein structure.
We have shown that the same diffusion coefficient ratios can be measured with an accuracy of 1% using a standard BPPLED pulse sequence, both for diamagnetic and paramagnetic systems, which allows for observing significant –though weak– variations when different species are interacting with the paramagnetic compound.

We have demonstrated that this approach is complementary to classical chemical shift titration experiments, and that it can be applied successfully to probe the supramolecular dynamic interactions between lanthanide complexes and small molecules on the one hand, or to determine rapidly their affinity for a targeted protein.

Metabolomics in the field of Health Sciences
We provide medical researchers with a better understanding, based on metabolomics by NMR, of the complex interplay between the different factors that contribute to the development of diseases.Recent progress in metabolomics has improved our understanding of the system-levels effect of metabolites in biofluids, cells and tissues, using either Mass Spectrometry and/or NMR as complementary detection techniques.
NMR is a highly versatile tool for obtaining metabolic profiles. It allows for analysing all the small metabolites simultaneously, with a high reproducibility. This technique is also non-destructive, robust and quantitative.
In this context, we have developed an expertise in deciphering the complex metabolic pathways that are involved in the evolution of diseases at every step of biological and medical research projects, from preliminary in vitro studies to clinical trials.  Our goal is notably to bring another vision that is complementary to transcriptomics or genomics and can contribute to establish pertinent biomarkers that will help to develop new diagnosis and prognosis approaches. We can help medical researchers to better understand the mechanism of action of new therapeutic approaches, by exploring how the metabolism is correlated to the response of patients to a given treatment. In this context, our group is also developing new analytical tools for boosting resolution and sensitivity of NMR analyses and thus paving the way for new therapeutic options.
Dissolution Dynamic Nuclear Polarization (D-DNP) of bio-samples.

Your content goes here. Edit or remove this text inline or in the module Content settings. You can also style every aspect of this content in the module Design settings and even apply custom CSS to this text in the module Advanced settings.

 

NMR Facility at UMR 8601

Our group is hosting the NMR facility of our Research Unit, including 3 NMR spectrometers (500 MHz to 600 MHz) and a prototype polarizer for Dissolution Dynamic Nuclear Polarization (D-DNP), to improve the sensitivity of solution NMR of bio-samples.

We are members of the Equipex program “CACSICE” (Center for the Analysis of Complex Systems in Complex Environments), and the Equipex program “Paris en resonance”, which provides access to DNP enhanced NMR equipment for users from both academic and industrial laboratories. We have also recently implemented the first NMR facility in France dedicated to metabolomic analyses for Health Sciences “Metabo Paris Santé”.

Publications

2021

3. Book Chapter: Analyse Métabolomique par Résonance Magnétique Nucléaire : Application aux Maladies Porphyriques
in La Révolution Biotechnologique et la médecine de demain 
Ducancel F., Schneider, B.
Doin Ed., ISBN: 978-2-7040-1620-4 (2021)

2. Capturing The Dynamic Association Between A Tris-Dipicolinate Lanthanide Complex And A Decapeptide: A Combined Paramagnetic NMR And Molecular Dynamics Exploration.
Denis-Quanquin, S., Bartocci, A., Szczepaniak, F., Riobé, F., Maury, O., Dumont, E.*, Giraud, N.*
Physical Chemistry Chemical Physics. (2021)
https://doi.org/10.1039/D0CP06570F

1. Solid-State versus Solution Investigation of a Luminescent Chiral BINOL-Derived Bisphosphate Single-Molecule Magnet
Mattei C.A., Montigaud, V., Gendron F., Denis-Quanquin S., Dorcet V., Giraud N., Riobé F., Argouarch G., Maury O., Le Guennic B.,* Cador O., Lalli C., Pointillart F.*
Inorg. Chem. Front., Advance Article (2021)
https://doi.org/10.1039/D0QI01192D

2020

5. NMR metabolomics study of follicular fluids reveals specific signature correlated to ART data in endometriosis patients
Pocate, K.; Santulli, P.; Kateb, F.; Bourdon, M.; Maignien, C.; Patrat, C.; Wolf, J.; Bertho, G.; Chapron, C.
Human Reproduction, Oxford Univ Press Great Clarendon St, Oxford OX2 6DP, England: 2020; pp 86-86.

4. Mn(I) Complex Redox Potential Tunability by Remote Lewis Acid Interaction.
Srinivasan, A. Campos, J., Giraud, N., Robert M. and Rivada-Wheelaghan O.* Dalton Trans., 2020,49, 16623-16626 (2020https://dx.doi.org/10.1039/D0DT02467H

3. The Follicular fluid metabolome differs according to the endometriosis phenotype.
Pocate-Cheriet, K., Santulli, P., Kateb, F., Bourdon, M., Maignien, C., Batteux, F., Chouzenoux, S., Patrat, C., Wolf, J.P., Bertho, G. & Chapron, C., Reproductive BioMedicine Online, 41, 1023-1037 (2020) https://doi.org/10.1016/j.rbmo.2020.09.002

2. Endometriosis Phenotypes Are Associated With Specific Serum Metabolic Profiles Determined By Proton-Nuclear Magnetic Resonance.
Maignien, C., Santulli, P., Kateb, F., Caradeuc, C., Marcellin, L., Pocate-Cheriet, K., Bourdon, M., Chouzenoux, S., Batteux, F., Bertho, G. & Chapron, C., Reproductive BioMedicine Online, 41, 640-652 (2020https://doi.org/10.1016/j.rbmo.2020.06.019

1. Multinuclear NMR in Polypeptide Liquid Crystals: Three Fertile Decades of Methodological Developments and Analytical Challenges.
Lesot, P.*, Aroulanda, C., Berdagué, P., Meddour, A., J., Merlet, D., Farjon, J., Giraud, N., & Lafon, O. Progress in Nuclear Magnetic Resonance Spectroscopy, 116, 85-154 (2019) https://dx.doi.org/10.1016/j.pnmrs.2019.10.001

2019
1. Monitoring Conformational Changes in an Enzyme Conversion Inhibitor Using Pure Shift Exchange NMR Spectroscopy. Aloui, G., Bouabdallah, S., Baltaze, J.P., Herbert Pucheta, J.E., Touil, S., Farjon, J. & Giraud, N.* ChemPhysChem, 20, 1738-1746 (2019) https://dx.doi.org/10.1002/cphc.201900244

2. A biomimetic strategy for the selective recognition of organophosphates in 100% water: synergies of electrostatic interactions, cavity embedment and metal coordination. Collin, S., Giraud, N., Dumont, E., & Reinaud, O.* Organic Chemistry Frontiers, 6, 1627-1636 (2019) https://dx.doi.org/10.1039/c9qo00263d

2018
1. Combining pure shift and J‐edited spectroscopies: A strategy for extracting chemical shifts and scalar couplings from highly crowded proton spectra of oligomeric saccharides. Pitoux, D., Hu, Z., Plainchont, B., Merlet, D., Farjon, J., Bonnaffé, D. & Giraud, N.* Magnetic Resonance in Chemistry, 56, 954-962 (2018) https://dx.doi.org/10.1002/mrc.4715

2. Highly Accurate Quantitative Analysis Of Enantiomeric Mixtures From Spatially Frequency Encoded 1H NMR Spectra. Plainchont, B., Pitoux, D., Cyrille, M. & Giraud, N.* Analytical Chemistry, 90, 1595-1600 (2018) https://dx.doi.org/10.1021/acs.analchem.7b02411

3. 1H NMR analyses of enantiomeric mixtures using chiral liquid crystals (invited paper). Farjon, J. & Giraud, N.* Current Opinion in Colloid and Interface Science, 33, 1-8 (2018) https://dx.doi.org/10.1016/j.cocis.2017.11.001

4. Bacterial Transferase MraY, a Source of Inspiration towards New Antibiotics, Mickaël J. Fer, Laurent Le Corre, Nicolas Pietrancosta, Nathalie Evrard-Todeschi, Samir Olatunji, Ahmed Bouhss, Sandrine Calvet-Vitale*,  Christine Gravier-Pelletier*. Current Medicinal Chemistry, 2018, 25 , Issue 42 , 2018 https://doi.org/10.2174/0929867325666180330095154

Till 2017
2017 

M Sarkis, MA Miteva, M Chiara Dasso Lang, M Jaouen, M-A Sari, M-O Galcéra, M Ethève-Quelquejeu, C Garbay, G Bertho*, E Braud* Insights into the interaction of high potency inhibitor IRC-083864 with phosphatase CDC25 : Binding model of CDC25 inhibitor IRC-083864 Proteins, 2017, Jan 5 doi: 101002/prot25236

M Melikian, B Eluard, G Bertho, V Baud, N Evrard-Todeschi Model of the Interaction between the NF-κB Inhibitory protein p100 and the E3 ubiquitin ligase β-TrCP based on NMR and Docking Experiments J Chem Inf Model, 2017 Jan 13 doi: 101021/acsjcim5b00409

Yurenko YP, Bazzi S, Marek R, Kozelka J Anion-π Interactions in Flavoproteins Involve a Substantial Charge-Transfer Component Chemistry 2017, 23 3246-3250

Kozelka J Lone pair-π interactions in biological systems: occurrence, function, and physical origin, Eur Biophys J 2017 May 2 doi: 101007/s00249-017-1210-1

R Balzan, L Fernandes, L Pidial, A Comment, B Tavitian, PR Vasos Pyruvate cellular uptake and enzymatic conversion probed by dissolution DNP‐NMR: the impact of overexpressed membrane transporters Magn Reson Chem, 2017, 55:579-583

 

2016

R Balzan, L Fernandes, A Comment, L Pidial, B Tavitian, PR Vasos Dissolution Dynamic Nuclear Polarization Instrumentation for Real-time Enzymatic Reaction Rate Measurements by NMR JoVE, 2016, e53548-e53548

M Luck, G Bertho, M Bateson, A Karras, A Yartseva, E Thervet, C Damon, N Pallet* Rule-Mining for the Early Prediction of Chronic Kidney Disease Based on Metabolomics and Multi-Source Data PLoS One 2016 Nov 18;11(11):e0166905

J-W Chiao, M Melikian, L Han, A Tsao, S K Mencher, J Fallon, G Bertho* & L G Wang* Interaction of a small molecule and STAT3-SH2 domain to block Y705 phosphorylation and inhibit lupus nephritis Biochem Pharmacol, 2016, 99, 123-131

Novotný J, Bazzi S, Marek R, Kozelka J Lone-pair-π interactions: analysis of the physical origin and biological implications Phys Chem Chem Phys 2016 Jul 28;18(28):19472-81

 

2015

I Anosova, S Melnik, K Tripsianes, F Kateb, I Grummt, M Sattler A novel RNA binding surface of the TAM domain of TIP5/BAZ2A mediates epigenetic regulation of rRNA genes Nucleic Acids Res 2015, 43, 5208-5220

Badri Z, Foroutan-Nejad C, Kozelka J, Marek R On the non-classical contribution in lone-pair-π interaction: IQA perspective Phys Chem Chem Phys 2015 Oct 21;17(39):26183-9

M Luck*, A Yartseva, G Bertho, E Thervet, P Beaune, N Pallet, C Damon Metabolic profiling of 1H NMR spectra in Chronic Kidney Disease with local predictive modeling Proc Int Conf Mach Learn Appl, 2015, 176-181

L Ducassou, F André, B Ramassamy, Y Xu-Li, M-A Loriot, P Beaune, G Bertho, M Lombard, D Mansuy, J-L Boucher Expression in Yeast and Discovery of New Substrates of Human Orphan Cytochrome P450 2U1: Interpretation of their Hydroxylation Regioselectivity from Docking Studies on a Protein 3D Model Biochim Biophys Acta 2015 ; 1850(7), 1426-37

 

2014

N Pallet, E Thervet, P Beaune, A Karras, G Bertho* The urinary metabolome of chronic kidney disease Kidney Int, 2014, 85, 1239–1240

M Carichon, N Pallet, C Schmitt, T Lefebvre, L Gouya, N Talbi, J-C Deybach, P Beaune, P Vasos, H Puy, G Bertho* The urinary metabolic fingerprint of Acute Intermittent Porphyria analyzed by 1H-NMR spectroscopy Anal Chem, 2014, 86, 2166−2174

S Téletchéa, V Stresing, S Hervouet, M Baud’huin, M-F Heymann, G Bertho, C Charrier, K Ando, D Heymann Novel RANK antagonists for the treatment of bone resorptive disease: Theoretical predictions and experimental validation J Bone Miner Res 2014, 29, 1466-1477

A Sadet, L Fernandes, F Kateb, R Balzan, PR Vasos Long-lived coherences: Improved dispersion in the frequency domain using continuous-wave and reduced-power windowed sustaining irradiation J Chem Phys 2014, 141 (5), 054203

 

2013

F Kateb, H Perrin, K Tripsianes, P Zou, R Spadaccini, M Bottomley, TM Franzmann, J Buchner,S Ansieau, M Sattler Structural and Functional Analysis of the DEAF-1 and BS69 MYND Domains PLoS One 2013, 8: e54715

L Fernandes, C Guerniou, I Marín‐Montesinos, M Pons, F Kateb, PR Vasos Long‐lived states in an intrinsically disordered protein domain Magn Reson Chem 2013, 51 (11), 729-733

C Decroos, V Balland, J-L Boucher, G Bertho, Y Xu, D Mansuy Towards Stable Electron Paramagnetic Resonance Oximetry Probes Synthesis, Characterization and Metabolic Evaluation of New Ester Derivatives of a Tris-(para-carboxyltetrathiaaryl)methyl (TAM) RadicalChem Res Toxicol, 2013, 26, 1561–1569

P Dansette, D Levent, A Hessani, G Bertho, D Mansuy Thiolactone Sulfoxides as New Reactive Metabolites Acting as Bis-Electrophiles: Implication in Clopidogrel and Prasugrel Bioactivation Chem Res Toxicol, 2013, 26, :794-802

C Charrier, G Bertho, O Petigny, P Moneton, R Azerad A new derivative detected in accelerated ageing of artesunate-amodiaquine fixed dose combination tablets J Pharm Biomed Anal 2013, 81-82:20-26

M Hamel, M Lecinq, M Gulea, J Kozelka Ortho-(methylsulfanyl) phenylphosphonates and derivatives: Synthesis and applications as mono-or bidentate ligands for the preparation of platinum complexes J Org Chem, 2013, Vol 745–746, 206–213

Bergès J, Fourré I, Pilmé J, Kozelka J Quantum chemical topology study of the water-platinum(II) interaction Inorg Chem 2013 Feb 4;52(3):1217-27

 

2012

T Suchánková, K Kubíček, J Kašpárková, V Brabec, J Kozelka Platinum–DNA interstrand crosslinks: Molecular determinants of bending and unwinding of the double helix J Inorg Biochem 2012 Mar;108:69-79

Monnet J, Kozelka J Cisplatin GG-crosslinks within single-stranded DNA: origin of the preference for left-handed helicity J Inorg Biochem 2012 Oct;115:106-12

A Mantsyzov, G Bouvier, N Evrard-Todeschi, G Bertho* Contact-based ligand-clustering approach for the identification of active compounds in virtual screening Adv Appl Bioinform Chem, 2012, doi:102147/AABCS30881

Fougeray, I Mami, G Bertho, C Legendre, P Beaune, E Thervet, N Pallet Tryptophan depletion and the kinase GCN2 mediate interferon γ-induced autophagy J Immunol, 2012, 189, 2954-2964

P Rada, A I Rojo, N Evrard-Todeschi, N G Innamorato, A Cotte, T Jaworski, J C Tobón-Velasco, H Devijver, M Flor García-Mayoral, F Van Leuven, J D Hayes, G Bertho*, A Cuadrado* Structural and functional characterization of Nrf2 degradation by the GSK-3/β-TrCP axis Mol Cell Biol, 2012, 32, 3486-3499

P Dansette, J Rosi, J Debernardi, G Bertho, D Mansuy Metabolic Activation of Prasugrel : Nature of the two Competitive Pathways Resulting in the Opening of its Thiophene RingChem Res Toxicol, 2012, 25, 1058–1065

C Chopard, T Prangé, G Bertho Naphthalene-dioxygenase catalysed cis-dihydroxylation of bicyclic azaarenes RSC Adv, 2012, 2, 605-615

PM Dansette, J Rosi, G Bertho, D Mansuy Cytochromes P450 Catalyze Both Steps of the Major Pathway of Clopidogrel Bioactivation Whereas Paraoxonase Catalyzes the Formation of a Minor Thiol Metabolite Isomer Chem Res Toxicol, 2012, 25, 348-356

 

2011

Kozelka, J* Evaluation of dissociation constants from competition binding experiments based on the relative binding ratio Anal Biochem, 2011,409, 66‐73

Kumpun, S ; Maria, A ; Crouzet, S ; Evrard‐Todeschi, N ; Girault, JP ; Lafont, R* Ecdysteroids from Chenopodium quinoa Willd, an ancient Andean crop of high nutritional value Food Chem, 2011, 125, 1226‐123

Kumpun, S ; Girault, JP ; Dinan, L ; Blais, C ; Maria, A ; Dauphin‐Villemant, C ; Yingyongnarongkul, B ; Suksamrarn, A ; Lafont, R* The metabolism of 20‐hydroxyecdysone in mice: relevance to pharmacological effects and gene switch applications of ecdysteroids. J Steroid Biochem Mol Biol, 2011, 126, 1‐9

Pons, J ; Tanchou, V ; Girault, JP ; Bertho, G ; Evrard‐Todeschi, N* NMR applications for identifying β‐TrCP protein‐ligand interactions Mini Rev Med Chem, 2011, 11, 283‐297

Sarkar, R ; Ahuja, P *; Vasos, PR ; Bornet, A ; Wagnieres, O ; Bodenhausen, G Long‐lived coherences for line‐narrowing in high‐field NMR Progr Nucl Magn Res Spectrosc, 2011, 59, 83‐9

Segawa, TF *; Bornet, A ; Salvi, N ; Mieville, P ; Vitzthum, V ; Carnevale, D ; Jannin, S ; Caporini, MA ; Ulzega, S ; Vasos, PR ; Rey, M ; Bodenhausen, G* Extending Timescales and Narrowing Linewidths in NMR Chimia, 2011, 65, 652‐655

Bornet, A ; Ahuja, P ; Sarkar, R ; Fernandes, L ; Hadji, S ; Lee, SY ; Haririnia, A ; Fushman, D ; Bodenhausen, G ; Vasos, PR* Long‐lived states to monitor protein unfolding by proton NMR Chem. Phys. Chem., 2011, 12, 2729‐2734

 

2010

Rizzato, S ; Bergès, J ; Mason, SA ; Albinati, A ; Kozelka, J* Dispersion‐driven hydrogen bonding: predicted hydrogen bond between water and platinum(II) identified by neutron diffraction Angew Chem Int Ed, 2010,49, 7440‐7443

Ahuja, P ; Sarkar, R ; Jannin, S ; Vasos, PR *; Bodenhausen, G  Proton hyperpolarisation preserved in long‐lived states  Chem Commun, 2010, 46, 8192‐8194

Mamadalieva, NZ ; Janibekov, AA ; Girault, JP ; Lafont, R*  Two minor phytoecdysteroids of the plant Silene viridiflora.  Nat Prod Commun, 2010, 5, 1579‐1582

Bouvier, G ; Evrard‐Todeschi, N ; Girault, JP ; Bertho, G* Automatic clustering of docking poses in virtual screening process using self‐organising map Bioinformatics, 2010, 26, 53‐60

 

2009

Kozelka, J*  Molecular origin of the sequence‐dependent kinetics of reactions between cisplatin derivatives and  DNA  Inorg Chim Acta, 2009,362, 651–668

Téletchéa, S ; Skauge, T ; Sletten, E ; Kozelka, J* Cisplatin Adducts on a GGG Sequence within a DNA Duplex Studied by NMR Spectroscopy and Molecular Dynamics Simulations Chem. Eur. J., 2009,15, 12320 – 12337

Crouzet, S ; Maria, A ; Dinan, L ; Lafont, R ; Girault, JP* Ecdysteroids from Cyanotis longifolia Benth. (Commelinaceae). Arch Insect Biochem Physiol, 2009, 72, 194‐209

Zibareva, L ; Yeriomina, VI ; Munkhjargal, N ; Girault, JP ; Dinan, L ; Lafont, R. * The phytoecdysteroid profiles of 7 species of Silene (Caryophyllaceae). Arch Insect Biochem Physiol, 2009, 72, 234‐248

 

2008

Ho, R ; Girault, JP ; Cousteau, PY ; Bianchini, JP ; Raharivelomanana, P ; Lafont, R* Isolation of a new class of ecdysteroid conjugates (glucosyl‐ferulates) using a combination of liquid chromatographic methods. J Chromatogr Sci, 2008, 46, 102‐110

Bertho, G *;. Bouvier, G ; Hui Bon Hoa, G ; Girault, JP* The key‐role of tyrosine 155 in the mechanism of prion transconformation as highlighted by a study of sheep mutant peptides. Peptides, 2008, 29, 1073‐1084

Pons, J ; Evrard‐Todeschi, N ; Bertho, G ; Gharbi‐Benarous, J ; Tanchou, V ; Benarous, R ; Girault, JP* Transfer‐NMR and Docking Studies Identify the Binding of the Peptide Derived from Activating Transcription Factor 4 to Protein Ubiquitin Ligase beta‐TrCP. Competition STD‐NMR with beta‐Catenin Biochemistry, 2008, 47, 14‐29 (Hot article)

Evrard‐Todeschi, N ; Pons, J ; Gharbi‐Benarous, J ; Bertho, G ; Benarous, R ; Girault, JP* Structure of the Complex between Phosphorylated Substrates and the beta‐TrCP Ubiquitine Ligase Receptor: A combined NMR, Molecular Modelling and Docking Approach J Chem Inf Model, 2008, 48, 2350‐2361

 

2007

Pons, J ; Evrard‐Todeschi, N ; Bertho, G ; Gharbi‐Benarous, J ; Sonois, V ; Benarous, R ; Girault, JP* Structural studies on 24P‐IkBa peptide derived from a human IkB‐a protein‐related with the inhibition of the transcription factor nuclear NFkB activity Biochemistry, 2007, 46, 2958‐2972

Pons, J ; Evrard‐Todeschi, N ; Bertho, G ; Gharbi‐Benarous, J ; Benarous, R ; Girault, JP* Phosphorylation‐Dependent Structure of ATF4 Peptides derived from a Human ATF4 Protein, a Member of the Family of Transcription Factors Peptides, 2007, 28, 2253‐2267

Snogan, E ; Vahirua‐Lechat, I ; Ho, R ; Bertho, G ; Girault, JP ; Ortiga, S ; Maria, A ; Lafont R* Ecdysteroids from the Medicinal Fern Microsorum scolopendria (Burm. f.) Phytochem Anal., 2007, 18, 441‐450

Aitken, DJ ; Albinati, A ; Gutier, A ; Husson, H‐P ; Morgant, G ; Nguyen‐Huy, D ; Kozelka, J *; Lemoine, P ; Ongeri, S ; Rizzato, S ; Viossat, B Platinum(II) and Palladium(II) Complexes with N‐Aminoguanidine Eur J Inorg Chem, 2007, 3327 ‐ 3334

Hamel, M ; Rizzato, S ; Lecinq, M ; Sene, A ; Vazeux, M ; Gulea, M ; Albinati, A ; Kozelka, J* Study of Intramolecular Competition between Carboxylate and Phosphonate for PtII with the Aid of a Novel Tridentate Carboxylato‐Thioether‐Phosphonato Ligand Chem. Eur. J., 2007,13, 5441‐5449

Nuclear Magnetic Resonance Spectroscopy

Team composition

Permanent Staff

N. Giraud, Pr

M. Baudin, IR
G. Bertho, IR
C. Caradeuc, AI
F. Kateb, MCU

Non permanent staff

C. Lucas-Torres

Students

X. Chen, PhD
K. Dos Santos, PhD

Team Description

The research group NMR of Biological Substances is part of the Team Bio-Spectroscopies. We develop analytical methods based on Nuclear Magnetic Resonance that we apply to the study of biological systems of major interest. Our research activity covers a wide range of projects ranging from the study of the interaction of small molecules with proteins, to the metabolomic analysis of biological fluids.

We design novel experiments to exceed the sensitivity and resolution limits of traditional NMR analyzes on complex samples. We are also working on the development of modelling and data analysis tools to make the best use of the information obtained on the biological systems under study. 

These projects are carried out in the frame of several collaborations with  laboratories working in the fields of organic chemistry, biochemistry, structural biology or medical research.

 

Research Themes

 

Methodological developments for ultra-high resolution NMR

We develop original concepts which aim at enhancing resolution in spectra of complex samples, to a point where their analysis becomes a faster, easier, and a more accurate process. 

Since the advent of Fourier transform NMR, a vast number of pulse sequences have been specifically designed, that allow to probe a great number of spin interactions on 1D and 2D spectra. Unfortunately, in most of the systems that are of interest to the scientific community nowadays especially in the biomedical field, the size or the complexity of the molecular architecture which is probed often leads to overcrowded spectra whose resolution is too low to give access to their analytical content.

In this context, we develop new analytical tools based on « pure shift » and « J-edited » NMR methods, and to apply them to challenging chemical and/or biological systems. Some of our most recent developments are described below. 

Pure Shift NMR applied to metabolomics analysis of cancer cells (coll. V. Baud and C. Thieblemont)

We have recently developed a “pure shift” version of the 1H 1D NOESY-presat experiment used for metabolomics. We have successfully applied it to an extra cellular medium taken from a cancer cell line. We have shown that we can detect metabolites in cancer cells, with a significant improvement of their spectral resolution, within an experimental time that is compatible with standard analytical workflows. The analysis of the resulting pure shift data obtained for a series of 40 Diffuse Large B-Cell (DLBCL) exo-metabolomes shows that we can observe individually about 85 % of the 40 metabolites usually reported in literature for extra cellular media in cancer studies. Furthermore, the statistical analyses performed on the “pure shift” dataset show that they are suitable for a clean separation of the groups of cells undergoing different anti-metabolic treatments, despite their lower sensitivity.

A) Pure shift and standard 1H NMR spectra (500 MHz) of an extra cellular medium from a DLBCL cell line treated with a combination of anti-metabolic drugs. B) Regions highlighting the resolution achieved in pure shift data for a collection of 40 DLBCL samples. C) Statistical analyses performed on “standard” and “pure shift” datasets.

Monitoring Conformational Changes in an Enzyme Conversion Inhibitor Using Pure Shift EXSY

We have also achieved recently the acquisition of 2D NMR EXSY spectra with ultrahigh resolution, which allowed us for probing the slow conformational exchange process in a pharmaceutical compound.

The resolution enhancement is achieved by implementing interferogram based PSYCHE homonuclear decoupling to generate a pure shift proton spectrum along the direct domain of the resulting data.

We have shown that although being less sensitive and requiring a longer acquisition time, the quality of pure shift spectra allows for extracting exchange rates values that are coherent with the ones determined by standard approach, on a temperature range that demonstrates the robustness of the chosen homonuclear decoupling method.

The resolution enhancement provided by the simplification of proton lineshape allows for probing a higher number of proton sites whose analysis would have been biased using a standard method. These results open the way to a thorough and accurate study of chemical exchange processes based on a multi-site analysis of  2D pure shift EXSY spectra

Dynamic and structural study of biomolecular interactions

Over the last years, our group has brought several contributions to the field of biomolecular interactions analysis. We develop experimental and theoretical methods for probing both dynamic and structural features of the supramolecular interactions that are underlying several biological processes. 

Describing and understanding supramolecular interactions in large biological or bio-mimetic systems has become a major stake over the recent years. However, despite the considerable progress that have been achieved in this field, probing at an atomic scale protein-protein, protein-nucleic acid, protein-lipid, protein-carbohydrate interactions, or the interactions with small molecules, enzyme substrates and regulators, still constitutes a critical challenge for chemists and biochemists.

Deciphering supramolecular interactions between lanthanide complexes and proteins

We have carried out a fruitful collaboration with the group of Dr. Olivier Maury (ENS de Lyon), to develop and understand the properties of Lanthanide derivatives that were shown to interact non-covalently with a broad range of proteins.

In this spirit, we had shown that some Tris(dipicolinate)-lanthanide complexes ([Ln(DPA)3]3- (DPA = dipicolinate = pyridine-2,6-dicarboxylate) interact strongly with specific amino-acids from the proteins, and thus can co-crystallize with them. This approach was demonstrated as a method of choice for incorporating a lanthanide derivative within the protein crystal, hereby exploiting their large anomalous signal for anomalous diffraction in crystallography, alongside with their well-known luminescence property. On the other hand, these lanthanide complexes have also been identified among the most promising non-covalent paramagnetic tags to probe the structure of proteins and peptides by NMR, both in solution and in the solid state. The analysis of the binding mode between [Ln(DPA)3]3- and the model proteins allowed us to evidence the existence of a supramolecular effect that mainly involves the tri-anionic complexes and cationic amino-acid residues. Notably, we had identified a preferential supramolecular interaction with arginine residues in protein systems over lysine and histidine, respectively.

Paramagnetic DOSY

Diffusion Ordered NMR SpectroscopY (DOSY) has been shown to be a method of choice for probing a wide range of molecular assemblies by measuring the rate at which they diffuse through the NMR sample, according to their size, or their interaction with their environment. We have implemented diffusion ordered NMR to determine accurately the mobility of paramagnetic tris-dipicolinate lanthanide complexes that are versatile probes of protein structure.
We have shown that the same diffusion coefficient ratios can be measured with an accuracy of 1% using a standard BPPLED pulse sequence, both for diamagnetic and paramagnetic systems, which allows for observing significant –though weak– variations when different species are interacting with the paramagnetic compound.

We have demonstrated that this approach is complementary to classical chemical shift titration experiments, and that it can be applied successfully to probe the supramolecular dynamic interactions between lanthanide complexes and small molecules on the one hand, or to determine rapidly their affinity for a targeted protein.

Metabolomics in the field of Health Sciences
We provide medical researchers with a better understanding, based on metabolomics by NMR, of the complex interplay between the different factors that contribute to the development of diseases.Recent progress in metabolomics has improved our understanding of the system-levels effect of metabolites in biofluids, cells and tissues, using either Mass Spectrometry and/or NMR as complementary detection techniques.
NMR is a highly versatile tool for obtaining metabolic profiles. It allows for analysing all the small metabolites simultaneously, with a high reproducibility. This technique is also non-destructive, robust and quantitative.
In this context, we have developed an expertise in deciphering the complex metabolic pathways that are involved in the evolution of diseases at every step of biological and medical research projects, from preliminary in vitro studies to clinical trials.  Our goal is notably to bring another vision that is complementary to transcriptomics or genomics and can contribute to establish pertinent biomarkers that will help to develop new diagnosis and prognosis approaches. We can help medical researchers to better understand the mechanism of action of new therapeutic approaches, by exploring how the metabolism is correlated to the response of patients to a given treatment. In this context, our group is also developing new analytical tools for boosting resolution and sensitivity of NMR analyses and thus paving the way for new therapeutic options.
Dissolution Dynamic Nuclear Polarization (D-DNP) of bio-samples.

Your content goes here. Edit or remove this text inline or in the module Content settings. You can also style every aspect of this content in the module Design settings and even apply custom CSS to this text in the module Advanced settings.

NMR Facility at UMR 8601

Our group is hosting the NMR facility of our Research Unit, including 3 NMR spectrometers (500 MHz to 600 MHz) and a prototype polarizer for Dissolution Dynamic Nuclear Polarization (D-DNP), to improve the sensitivity of solution NMR of bio-samples.

We are members of the Equipex program “CACSICE” (Center for the Analysis of Complex Systems in Complex Environments), and the Equipex program “Paris en resonance”, which provides access to DNP enhanced NMR equipment for users from both academic and industrial laboratories. We have also recently implemented the first NMR facility in France dedicated to metabolomic analyses for Health Sciences “Metabo Paris Santé”.

2021

3. Book Chapter: Analyse Métabolomique par Résonance Magnétique Nucléaire : Application aux Maladies Porphyriques
in La Révolution Biotechnologique et la médecine de demain 
Ducancel F., Schneider, B.
Doin Ed., ISBN: 978-2-7040-1620-4 (2021)

2. Capturing The Dynamic Association Between A Tris-Dipicolinate Lanthanide Complex And A Decapeptide: A Combined Paramagnetic NMR And Molecular Dynamics Exploration.
Denis-Quanquin, S., Bartocci, A., Szczepaniak, F., Riobé, F., Maury, O., Dumont, E.*, Giraud, N.*
Physical Chemistry Chemical Physics. (2021)
https://doi.org/10.1039/D0CP06570F

1. Solid-State versus Solution Investigation of a Luminescent Chiral BINOL-Derived Bisphosphate Single-Molecule Magnet
Mattei C.A., Montigaud, V., Gendron F., Denis-Quanquin S., Dorcet V., Giraud N., Riobé F., Argouarch G., Maury O., Le Guennic B.,* Cador O., Lalli C., Pointillart F.*
Inorg. Chem. Front., Advance Article (2021)
https://doi.org/10.1039/D0QI01192D

2020

5. NMR metabolomics study of follicular fluids reveals specific signature correlated to ART data in endometriosis patients
Pocate, K.; Santulli, P.; Kateb, F.; Bourdon, M.; Maignien, C.; Patrat, C.; Wolf, J.; Bertho, G.; Chapron, C.
Human Reproduction, Oxford Univ Press Great Clarendon St, Oxford OX2 6DP, England: 2020; pp 86-86.

4. Mn(I) Complex Redox Potential Tunability by Remote Lewis Acid Interaction.
Srinivasan, A. Campos, J., Giraud, N., Robert M. and Rivada-Wheelaghan O.* Dalton Trans., 2020,49, 16623-16626 (2020https://dx.doi.org/10.1039/D0DT02467H

3. The Follicular fluid metabolome differs according to the endometriosis phenotype.
Pocate-Cheriet, K., Santulli, P., Kateb, F., Bourdon, M., Maignien, C., Batteux, F., Chouzenoux, S., Patrat, C., Wolf, J.P., Bertho, G. & Chapron, C., Reproductive BioMedicine Online, 41, 1023-1037 (2020) https://doi.org/10.1016/j.rbmo.2020.09.002

2. Endometriosis Phenotypes Are Associated With Specific Serum Metabolic Profiles Determined By Proton-Nuclear Magnetic Resonance.
Maignien, C., Santulli, P., Kateb, F., Caradeuc, C., Marcellin, L., Pocate-Cheriet, K., Bourdon, M., Chouzenoux, S., Batteux, F., Bertho, G. & Chapron, C., Reproductive BioMedicine Online, 41, 640-652 (2020https://doi.org/10.1016/j.rbmo.2020.06.019

1. Multinuclear NMR in Polypeptide Liquid Crystals: Three Fertile Decades of Methodological Developments and Analytical Challenges.
Lesot, P.*, Aroulanda, C., Berdagué, P., Meddour, A., J., Merlet, D., Farjon, J., Giraud, N., & Lafon, O. Progress in Nuclear Magnetic Resonance Spectroscopy, 116, 85-154 (2019) https://dx.doi.org/10.1016/j.pnmrs.2019.10.001

2019
1. Monitoring Conformational Changes in an Enzyme Conversion Inhibitor Using Pure Shift Exchange NMR Spectroscopy. Aloui, G., Bouabdallah, S., Baltaze, J.P., Herbert Pucheta, J.E., Touil, S., Farjon, J. & Giraud, N.* ChemPhysChem, 20, 1738-1746 (2019) https://dx.doi.org/10.1002/cphc.201900244

2. A biomimetic strategy for the selective recognition of organophosphates in 100% water: synergies of electrostatic interactions, cavity embedment and metal coordination. Collin, S., Giraud, N., Dumont, E., & Reinaud, O.* Organic Chemistry Frontiers, 6, 1627-1636 (2019) https://dx.doi.org/10.1039/c9qo00263d

2018
1. Combining pure shift and J‐edited spectroscopies: A strategy for extracting chemical shifts and scalar couplings from highly crowded proton spectra of oligomeric saccharides. Pitoux, D., Hu, Z., Plainchont, B., Merlet, D., Farjon, J., Bonnaffé, D. & Giraud, N.* Magnetic Resonance in Chemistry, 56, 954-962 (2018) https://dx.doi.org/10.1002/mrc.4715

2. Highly Accurate Quantitative Analysis Of Enantiomeric Mixtures From Spatially Frequency Encoded 1H NMR Spectra. Plainchont, B., Pitoux, D., Cyrille, M. & Giraud, N.* Analytical Chemistry, 90, 1595-1600 (2018) https://dx.doi.org/10.1021/acs.analchem.7b02411

3. 1H NMR analyses of enantiomeric mixtures using chiral liquid crystals (invited paper). Farjon, J. & Giraud, N.* Current Opinion in Colloid and Interface Science, 33, 1-8 (2018) https://dx.doi.org/10.1016/j.cocis.2017.11.001

4. Bacterial Transferase MraY, a Source of Inspiration towards New Antibiotics, Mickaël J. Fer, Laurent Le Corre, Nicolas Pietrancosta, Nathalie Evrard-Todeschi, Samir Olatunji, Ahmed Bouhss, Sandrine Calvet-Vitale*,  Christine Gravier-Pelletier*. Current Medicinal Chemistry, 2018, 25 , Issue 42 , 2018 https://doi.org/10.2174/0929867325666180330095154

Till 2017
2017 

M Sarkis, MA Miteva, M Chiara Dasso Lang, M Jaouen, M-A Sari, M-O Galcéra, M Ethève-Quelquejeu, C Garbay, G Bertho*, E Braud* Insights into the interaction of high potency inhibitor IRC-083864 with phosphatase CDC25 : Binding model of CDC25 inhibitor IRC-083864 Proteins, 2017, Jan 5 doi: 101002/prot25236

M Melikian, B Eluard, G Bertho, V Baud, N Evrard-Todeschi Model of the Interaction between the NF-κB Inhibitory protein p100 and the E3 ubiquitin ligase β-TrCP based on NMR and Docking Experiments J Chem Inf Model, 2017 Jan 13 doi: 101021/acsjcim5b00409

Yurenko YP, Bazzi S, Marek R, Kozelka J Anion-π Interactions in Flavoproteins Involve a Substantial Charge-Transfer Component Chemistry 2017, 23 3246-3250

Kozelka J Lone pair-π interactions in biological systems: occurrence, function, and physical origin, Eur Biophys J 2017 May 2 doi: 101007/s00249-017-1210-1

R Balzan, L Fernandes, L Pidial, A Comment, B Tavitian, PR Vasos Pyruvate cellular uptake and enzymatic conversion probed by dissolution DNP‐NMR: the impact of overexpressed membrane transporters Magn Reson Chem, 2017, 55:579-583

 

2016

R Balzan, L Fernandes, A Comment, L Pidial, B Tavitian, PR Vasos Dissolution Dynamic Nuclear Polarization Instrumentation for Real-time Enzymatic Reaction Rate Measurements by NMR JoVE, 2016, e53548-e53548

M Luck, G Bertho, M Bateson, A Karras, A Yartseva, E Thervet, C Damon, N Pallet* Rule-Mining for the Early Prediction of Chronic Kidney Disease Based on Metabolomics and Multi-Source Data PLoS One 2016 Nov 18;11(11):e0166905

J-W Chiao, M Melikian, L Han, A Tsao, S K Mencher, J Fallon, G Bertho* & L G Wang* Interaction of a small molecule and STAT3-SH2 domain to block Y705 phosphorylation and inhibit lupus nephritis Biochem Pharmacol, 2016, 99, 123-131

Novotný J, Bazzi S, Marek R, Kozelka J Lone-pair-π interactions: analysis of the physical origin and biological implications Phys Chem Chem Phys 2016 Jul 28;18(28):19472-81

 

2015

I Anosova, S Melnik, K Tripsianes, F Kateb, I Grummt, M Sattler A novel RNA binding surface of the TAM domain of TIP5/BAZ2A mediates epigenetic regulation of rRNA genes Nucleic Acids Res 2015, 43, 5208-5220

Badri Z, Foroutan-Nejad C, Kozelka J, Marek R On the non-classical contribution in lone-pair-π interaction: IQA perspective Phys Chem Chem Phys 2015 Oct 21;17(39):26183-9

M Luck*, A Yartseva, G Bertho, E Thervet, P Beaune, N Pallet, C Damon Metabolic profiling of 1H NMR spectra in Chronic Kidney Disease with local predictive modeling Proc Int Conf Mach Learn Appl, 2015, 176-181

L Ducassou, F André, B Ramassamy, Y Xu-Li, M-A Loriot, P Beaune, G Bertho, M Lombard, D Mansuy, J-L Boucher Expression in Yeast and Discovery of New Substrates of Human Orphan Cytochrome P450 2U1: Interpretation of their Hydroxylation Regioselectivity from Docking Studies on a Protein 3D Model Biochim Biophys Acta 2015 ; 1850(7), 1426-37

 

2014

N Pallet, E Thervet, P Beaune, A Karras, G Bertho* The urinary metabolome of chronic kidney disease Kidney Int, 2014, 85, 1239–1240

M Carichon, N Pallet, C Schmitt, T Lefebvre, L Gouya, N Talbi, J-C Deybach, P Beaune, P Vasos, H Puy, G Bertho* The urinary metabolic fingerprint of Acute Intermittent Porphyria analyzed by 1H-NMR spectroscopy Anal Chem, 2014, 86, 2166−2174

S Téletchéa, V Stresing, S Hervouet, M Baud’huin, M-F Heymann, G Bertho, C Charrier, K Ando, D Heymann Novel RANK antagonists for the treatment of bone resorptive disease: Theoretical predictions and experimental validation J Bone Miner Res 2014, 29, 1466-1477

A Sadet, L Fernandes, F Kateb, R Balzan, PR Vasos Long-lived coherences: Improved dispersion in the frequency domain using continuous-wave and reduced-power windowed sustaining irradiation J Chem Phys 2014, 141 (5), 054203

 

2013

F Kateb, H Perrin, K Tripsianes, P Zou, R Spadaccini, M Bottomley, TM Franzmann, J Buchner,S Ansieau, M Sattler Structural and Functional Analysis of the DEAF-1 and BS69 MYND Domains PLoS One 2013, 8: e54715

L Fernandes, C Guerniou, I Marín‐Montesinos, M Pons, F Kateb, PR Vasos Long‐lived states in an intrinsically disordered protein domain Magn Reson Chem 2013, 51 (11), 729-733

C Decroos, V Balland, J-L Boucher, G Bertho, Y Xu, D Mansuy Towards Stable Electron Paramagnetic Resonance Oximetry Probes Synthesis, Characterization and Metabolic Evaluation of New Ester Derivatives of a Tris-(para-carboxyltetrathiaaryl)methyl (TAM) RadicalChem Res Toxicol, 2013, 26, 1561–1569

P Dansette, D Levent, A Hessani, G Bertho, D Mansuy Thiolactone Sulfoxides as New Reactive Metabolites Acting as Bis-Electrophiles: Implication in Clopidogrel and Prasugrel Bioactivation Chem Res Toxicol, 2013, 26, :794-802

C Charrier, G Bertho, O Petigny, P Moneton, R Azerad A new derivative detected in accelerated ageing of artesunate-amodiaquine fixed dose combination tablets J Pharm Biomed Anal 2013, 81-82:20-26

M Hamel, M Lecinq, M Gulea, J Kozelka Ortho-(methylsulfanyl) phenylphosphonates and derivatives: Synthesis and applications as mono-or bidentate ligands for the preparation of platinum complexes J Org Chem, 2013, Vol 745–746, 206–213

Bergès J, Fourré I, Pilmé J, Kozelka J Quantum chemical topology study of the water-platinum(II) interaction Inorg Chem 2013 Feb 4;52(3):1217-27

 

2012

T Suchánková, K Kubíček, J Kašpárková, V Brabec, J Kozelka Platinum–DNA interstrand crosslinks: Molecular determinants of bending and unwinding of the double helix J Inorg Biochem 2012 Mar;108:69-79

Monnet J, Kozelka J Cisplatin GG-crosslinks within single-stranded DNA: origin of the preference for left-handed helicity J Inorg Biochem 2012 Oct;115:106-12

A Mantsyzov, G Bouvier, N Evrard-Todeschi, G Bertho* Contact-based ligand-clustering approach for the identification of active compounds in virtual screening Adv Appl Bioinform Chem, 2012, doi:102147/AABCS30881

Fougeray, I Mami, G Bertho, C Legendre, P Beaune, E Thervet, N Pallet Tryptophan depletion and the kinase GCN2 mediate interferon γ-induced autophagy J Immunol, 2012, 189, 2954-2964

P Rada, A I Rojo, N Evrard-Todeschi, N G Innamorato, A Cotte, T Jaworski, J C Tobón-Velasco, H Devijver, M Flor García-Mayoral, F Van Leuven, J D Hayes, G Bertho*, A Cuadrado* Structural and functional characterization of Nrf2 degradation by the GSK-3/β-TrCP axis Mol Cell Biol, 2012, 32, 3486-3499

P Dansette, J Rosi, J Debernardi, G Bertho, D Mansuy Metabolic Activation of Prasugrel : Nature of the two Competitive Pathways Resulting in the Opening of its Thiophene RingChem Res Toxicol, 2012, 25, 1058–1065

C Chopard, T Prangé, G Bertho Naphthalene-dioxygenase catalysed cis-dihydroxylation of bicyclic azaarenes RSC Adv, 2012, 2, 605-615

PM Dansette, J Rosi, G Bertho, D Mansuy Cytochromes P450 Catalyze Both Steps of the Major Pathway of Clopidogrel Bioactivation Whereas Paraoxonase Catalyzes the Formation of a Minor Thiol Metabolite Isomer Chem Res Toxicol, 2012, 25, 348-356

 

2011

Kozelka, J* Evaluation of dissociation constants from competition binding experiments based on the relative binding ratio Anal Biochem, 2011,409, 66‐73

Kumpun, S ; Maria, A ; Crouzet, S ; Evrard‐Todeschi, N ; Girault, JP ; Lafont, R* Ecdysteroids from Chenopodium quinoa Willd, an ancient Andean crop of high nutritional value Food Chem, 2011, 125, 1226‐123

Kumpun, S ; Girault, JP ; Dinan, L ; Blais, C ; Maria, A ; Dauphin‐Villemant, C ; Yingyongnarongkul, B ; Suksamrarn, A ; Lafont, R* The metabolism of 20‐hydroxyecdysone in mice: relevance to pharmacological effects and gene switch applications of ecdysteroids. J Steroid Biochem Mol Biol, 2011, 126, 1‐9

Pons, J ; Tanchou, V ; Girault, JP ; Bertho, G ; Evrard‐Todeschi, N* NMR applications for identifying β‐TrCP protein‐ligand interactions Mini Rev Med Chem, 2011, 11, 283‐297

Sarkar, R ; Ahuja, P *; Vasos, PR ; Bornet, A ; Wagnieres, O ; Bodenhausen, G Long‐lived coherences for line‐narrowing in high‐field NMR Progr Nucl Magn Res Spectrosc, 2011, 59, 83‐9

Segawa, TF *; Bornet, A ; Salvi, N ; Mieville, P ; Vitzthum, V ; Carnevale, D ; Jannin, S ; Caporini, MA ; Ulzega, S ; Vasos, PR ; Rey, M ; Bodenhausen, G* Extending Timescales and Narrowing Linewidths in NMR Chimia, 2011, 65, 652‐655

Bornet, A ; Ahuja, P ; Sarkar, R ; Fernandes, L ; Hadji, S ; Lee, SY ; Haririnia, A ; Fushman, D ; Bodenhausen, G ; Vasos, PR* Long‐lived states to monitor protein unfolding by proton NMR Chem. Phys. Chem., 2011, 12, 2729‐2734

 

2010

Rizzato, S ; Bergès, J ; Mason, SA ; Albinati, A ; Kozelka, J* Dispersion‐driven hydrogen bonding: predicted hydrogen bond between water and platinum(II) identified by neutron diffraction Angew Chem Int Ed, 2010,49, 7440‐7443

Ahuja, P ; Sarkar, R ; Jannin, S ; Vasos, PR *; Bodenhausen, G  Proton hyperpolarisation preserved in long‐lived states  Chem Commun, 2010, 46, 8192‐8194

Mamadalieva, NZ ; Janibekov, AA ; Girault, JP ; Lafont, R*  Two minor phytoecdysteroids of the plant Silene viridiflora.  Nat Prod Commun, 2010, 5, 1579‐1582

Bouvier, G ; Evrard‐Todeschi, N ; Girault, JP ; Bertho, G* Automatic clustering of docking poses in virtual screening process using self‐organising map Bioinformatics, 2010, 26, 53‐60

 

2009

Kozelka, J*  Molecular origin of the sequence‐dependent kinetics of reactions between cisplatin derivatives and  DNA  Inorg Chim Acta, 2009,362, 651–668

Téletchéa, S ; Skauge, T ; Sletten, E ; Kozelka, J* Cisplatin Adducts on a GGG Sequence within a DNA Duplex Studied by NMR Spectroscopy and Molecular Dynamics Simulations Chem. Eur. J., 2009,15, 12320 – 12337

Crouzet, S ; Maria, A ; Dinan, L ; Lafont, R ; Girault, JP* Ecdysteroids from Cyanotis longifolia Benth. (Commelinaceae). Arch Insect Biochem Physiol, 2009, 72, 194‐209

Zibareva, L ; Yeriomina, VI ; Munkhjargal, N ; Girault, JP ; Dinan, L ; Lafont, R. * The phytoecdysteroid profiles of 7 species of Silene (Caryophyllaceae). Arch Insect Biochem Physiol, 2009, 72, 234‐248

 

2008

Ho, R ; Girault, JP ; Cousteau, PY ; Bianchini, JP ; Raharivelomanana, P ; Lafont, R* Isolation of a new class of ecdysteroid conjugates (glucosyl‐ferulates) using a combination of liquid chromatographic methods. J Chromatogr Sci, 2008, 46, 102‐110

Bertho, G *;. Bouvier, G ; Hui Bon Hoa, G ; Girault, JP* The key‐role of tyrosine 155 in the mechanism of prion transconformation as highlighted by a study of sheep mutant peptides. Peptides, 2008, 29, 1073‐1084

Pons, J ; Evrard‐Todeschi, N ; Bertho, G ; Gharbi‐Benarous, J ; Tanchou, V ; Benarous, R ; Girault, JP* Transfer‐NMR and Docking Studies Identify the Binding of the Peptide Derived from Activating Transcription Factor 4 to Protein Ubiquitin Ligase beta‐TrCP. Competition STD‐NMR with beta‐Catenin Biochemistry, 2008, 47, 14‐29 (Hot article)

Evrard‐Todeschi, N ; Pons, J ; Gharbi‐Benarous, J ; Bertho, G ; Benarous, R ; Girault, JP* Structure of the Complex between Phosphorylated Substrates and the beta‐TrCP Ubiquitine Ligase Receptor: A combined NMR, Molecular Modelling and Docking Approach J Chem Inf Model, 2008, 48, 2350‐2361

 

2007

Pons, J ; Evrard‐Todeschi, N ; Bertho, G ; Gharbi‐Benarous, J ; Sonois, V ; Benarous, R ; Girault, JP* Structural studies on 24P‐IkBa peptide derived from a human IkB‐a protein‐related with the inhibition of the transcription factor nuclear NFkB activity Biochemistry, 2007, 46, 2958‐2972

Pons, J ; Evrard‐Todeschi, N ; Bertho, G ; Gharbi‐Benarous, J ; Benarous, R ; Girault, JP* Phosphorylation‐Dependent Structure of ATF4 Peptides derived from a Human ATF4 Protein, a Member of the Family of Transcription Factors Peptides, 2007, 28, 2253‐2267

Snogan, E ; Vahirua‐Lechat, I ; Ho, R ; Bertho, G ; Girault, JP ; Ortiga, S ; Maria, A ; Lafont R* Ecdysteroids from the Medicinal Fern Microsorum scolopendria (Burm. f.) Phytochem Anal., 2007, 18, 441‐450

Aitken, DJ ; Albinati, A ; Gutier, A ; Husson, H‐P ; Morgant, G ; Nguyen‐Huy, D ; Kozelka, J *; Lemoine, P ; Ongeri, S ; Rizzato, S ; Viossat, B Platinum(II) and Palladium(II) Complexes with N‐Aminoguanidine Eur J Inorg Chem, 2007, 3327 ‐ 3334

Hamel, M ; Rizzato, S ; Lecinq, M ; Sene, A ; Vazeux, M ; Gulea, M ; Albinati, A ; Kozelka, J* Study of Intramolecular Competition between Carboxylate and Phosphonate for PtII with the Aid of a Novel Tridentate Carboxylato‐Thioether‐Phosphonato Ligand Chem. Eur. J., 2007,13, 5441‐5449