Gildas Bertho- PhD
- Head of NMR facilities at Université Paris Cité
Gildas Bertho
- PhD
- Head of NMR facilities at Université Paris Cité
About
132
Publications
18,037
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
2,232
Citations
Introduction
From the identification of ligands of macromolecules to their follow up in cells by NMR
Current institution
Additional affiliations
Position
- Head of Department
September 1998 - present
Position
- Research Ingeneer
Publications
Publications (132)
Background
Methylglyoxal (MGO) is a potent glycating agent that contributes to the pathogenesis of diabetes. However, MGO is unstable in plasma without demanding sample preparation at blood collection, limiting its clinical utility as a biomarker. We aimed to discover reliable MGO-glycated albumin (ALB)-derived biomarkers and to assess their associ...
Persistent organic pollutants (POPs) are associated with many adverse health effects in humans, including cancers, immune, reproductive, neurological disorders and metabolic diseases. These chemicals are known to accumulate in fatty tissues, from which they can be released in other tissue compartments of living organisms, in particular, upon weight...
Background/Objectives: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, characterized by aggressive and heterogeneous tumors originating from B-cells. Especially in patients with relapsed or refractory (R/R) disease, DLBCL remains a challenging cancer to treat. Metabolic reprogramming is a hallmark of malignant...
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, characterized by aggressive and heterogeneous tumors originating from B-cells. Especially in patients with relapsed or refractory (R/R) disease, DLBCL remains a challenging cancer to treat. Metabolic reprogramming is a hallmark of malignant cells. Our research fo...
Cancer cells reprogram their metabolism to fulfill their high energetic demand. Lipid metabolism is most often reprogrammed for cancer cell survival and tumor development. The role of alternative oncogenic NF-κB/RelB subunit in the reprogramming of lipid metabolism in cancer is unknown. Here we report that RelB plays a central role at the crossroad...
Gastrointestinal parasitism is a major health and welfare problem in ruminants. Synthetic chemical anthelmintic drugs have led to the emergence of resistance in gastrointestinal strongyles, inducing the search for alternatives to control the infections that affect ruminants. The objective of this work was to evaluate the anthelmintic potential of p...
Background
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease that commonly results from a high-calorie diet and sedentary lifestyle, leading to insulin resistance and glucose homeostasis perturbation. Physical activity is recommended as one first-line treatment in T2DM, but it leads to contrasted results. We hypothesized that, instead...
![Figure 5. 3D densities (in points.Å −3 ) of [Ln(DPA) 3 ] 3-(left panel)...](publication/380275132/figure/fig3/AS:11431281240161509@1714657069871/D-densities-in-pointsA-3-of-LnDPA-3-3-left-panel-and-LnXo4-LnXo4-right_Q320.jpg)
The supramolecular interaction between lanthanide complexes and proteins is at the heart of numerous chemical and biological studies. Some of these complexes have demonstrated remarkable interaction properties with proteins or...
Background: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease that commonly results from a high-calorie diet and sedentary lifestyle, leading to insulin resistance and glucose homeostasis perturbation. Physical activity is recommended as one first-line treatment in T2DM, but it leads to contrasted results. We hypothesized that, instead...
The supramolecular interaction between lanthanide complexes and proteins is at the heart of numerous chemical and biological studies. Some of these complexes have demonstrated remarkable interaction properties with proteins or peptides in solution and in the crystalline state. Here we have used the paramagnetism of lanthanide ions to characterize t...
Nowadays, exposure to endocrine-disrupting chemicals (EDCs), including persistent organic pollutants (POPs), is one of the most critical threats to public health. EDCs are chemicals that mimic, block, or interfere with hormones in the body's endocrine system and have been associated with a wide range of health issues. This innovative, untargeted me...
NMR is one of the most powerful techniques for the analysis of biological samples in the field of metabolomics. However, the high complexity of fluids, tissues or other biological materials taken from living organisms is still a challenge for state-of-the-art pulse sequences, thereby limiting the detection, the identification, and the quantificatio...
Glutamine is under scrutiny regarding its metabolic deregulation linked to energetic reprogramming in cancer cells. Many analytical techniques have been used to better understand the impact of the metabolism of amino acids on biological processes, however only a few are suited to work with complex samples. Here, we report the use of a general disso...
Accurate quantification of metabolites by nuclear magnetic resonance (NMR) is of prime importance in the field of health sciences for understanding the metabolic pathways of the investigated system, to address the mechanisms of action of diseases, and improving their diagnosis, treatment, and prognosis. Unfortunately, the absolute quantitative anal...
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy derived from early T cell progenitors. Since relapsed T-ALL is associated with a poor prognosis improving initial treatment of patients is essential to avoid resistant selection of T-ALL. During initiation, development, metastasis and even in response to chemotherap...
Eighteen (18) new N‐acylhydrazones (9a‐r) containing the imidazo[1,2‐a]pyridine scaffold were synthesized through a seven steps reaction sequence, ending with a condensation of 2‐(3‐nitro‐H‐imidazo[1,2‐a]pyridin‐2‐ylthio)acetohydrazide with various benzaldehyde derivatives (8a‐r). All synthesized compounds were characterized by 1D NMR (1H and 13C N...
We report the analysis of complex samples obtained during the microwave irradiation/heating of Norbixin, which has been identified as a potential therapeutic target for age‐related macular degeneration (AMD). In this context identifying the different isomers that are obtained during its degradation is of primary importance. However, this characteri...
The synergistic functioning of redox‐active components that emerges from prototypical 2,2′‐di(N‐methylpyrid‐4‐ylium)‐1,1′‐biphenyl is described. Interestingly, even if a trans conformation of the native assembly is expected, due to electrostatic repulsion between cationic pyridinium units, we demonstrate that cis conformation is equally energy‐stab...
Corruption of cellular prion protein (PrPC) function(s) at the plasma membrane of neurons is at the root of prion diseases, such as Creutzfeldt-Jakob disease and its variant in humans, and Bovine Spongiform Encephalopathies, better known as mad cow disease, in cattle. The roles exerted by PrPC, however, remain poorly elucidated. With the perspectiv...
Specific inhibition of NADPH oxidases (NOX) and NO-synthases (NOS), two enzymes associated with redox stress in tumor cells, has aroused great pharmacological interest. Here, we show how these enzymes distinguish between isomeric 2′- and 3′-phosphate derivatives, a difference used to improve the specificity of inhibition by isolated 2′- and 3′-phos...
Ecdysteroids are not endogenous to mammals, but are normal components of the food intake of many mammalian species consuming phytoecdysteroid-containing plants. The most frequently encountered phytoecdysteroid is 20-hydroxyecdysone (20E). Several pharmaceutical effects have been observed after ecdysteroid injection or ingestion, but it is not clear...
Objective
To determine whether the adenomyosis phenotype affects the proton nuclear magnetic resonance (¹H-NMR)-based serum metabolic profile of patients.
Design
Cohort study.
Setting
University hospital-based research center.
Patients
Seventy-seven patients who underwent laparoscopy for a benign gynecologic condition.
Interventions
Pelvic magn...
Background: Tetrahydrothienopyridines Ticlopidine (Ticlid) and Clopidogrel (Plavix) and Prasugrel are prodrug antagonists of the platelets ADP receptor P2Y12. They are transformed in vivo into a pharmacologically active 4-mercapto-3-piperidinylidene-acetic acid derivative by two successive cytochrome P450 dependent reactions (1-3). The first interm...
Research question:
Is there a follicular fluid-specific metabolic profile in deep infiltrating endometriosis (DIE) depending on the presence of an associated ovarian endometrioma (OMA) that could lead to the identification of biomarkers for diagnosis and prognosis of the disease?
Design:
In this prospective cohort study, proton nuclear magnetic...
Research question: To determine if there is a correlation between the serum metabolic profile and the endometriosis phenotype.
Design: This was a pilot study nestled in a prospective cohort study at a University hospital, including forty-six patients with painful endometriosis who had surgery, and 21 controls who did not have macroscopic endometrio...
The article Urinary metabolic profiling of asymptomatic acute intermittent porphyria using a rule-mining-based algorithm, written by Margaux Luck, Caroline Schmitt, Neila Talbi, Laurent Gouya, Cédric Caradeuc, Hervé Puy, Gildas Bertho and Nicolas Pallet was originally published Online First without open access. After publication in volume [14], iss...
Introduction
Metabolomic profiling combines Nuclear Magnetic Resonance spectroscopy with supervised statistical analysis that might allow to better understanding the mechanisms of a disease.
Objectives
In this study, the urinary metabolic profiling of individuals with porphyrias was performed to predict different types of disease, and to propose n...
Many stressors that are encountered upon kidney injury are likely to trigger endoplasmic reticulum (ER) stress, subsequently activating transcriptional, translational and metabolic reprogramming. Monitoring early cellular adaptive responses engaged after hemodynamic impairment yields may represent a clinically relevant approach. However, a non-inva...
Amyotrophic Lateral Sclerosis is an adult-onset neurodegenerative disease characterized by the specific loss of motor neurons, leading to muscle paralysis and death. Although the cellular mechanisms underlying amyotrophic lateral sclerosis (ALS)-induced toxicity for motor neurons remain poorly understood, growing evidence suggest a defective energe...
CDC25 phosphatases play a crucial role in cell cycle regulation. They have been found to be over-expressed in various human tumours and to be valuable targets for cancer treatment. Here, we report the first model of binding of the most potent CDC25 inhibitor to date, the bis-quinone IRC-083864, into CDC25B obtained by combining molecular modelling...
NF-κB is a major transcription factor whose activation is triggered through two main activation pathways: the canonical pathway involving disruption of IκB-α/NF-κB complexes and the alternative pathway whose activation relies on the inducible proteolysis of the inhibitory protein p100. One central step controlling p100 processing consists in the in...
H Nuclear Magnetic Resonance (NMR)-based metabolic profiling is very promising for the diagnostic of the stages of chronic kidney disease (CKD). Because of the high dimension of NMR spectra datasets and the complex mixture of metabolites in biological samples, the identification of discriminant biomarkers of a disease is challenging. None of the wi...
Steps of the supervised rule mining algorithm: an example with the 1D rule case.
(A) Step 1: Exhaustive rule generation and selection. A segment represents a 1D rule defined by its feature condition FC (i.e., range of variable bins on x-axis). Selected rules called candidates rules (circled) have, for one of the two modalities a rule modality size...
Data used for the supervised analysis.
In sheet 1 is provided the discretized data used for the supervised analysis and in sheet 2 the related metadata.
(XLS)
Cytochrome P450 2U1 (CYP2U1) has been identified from the human genome and is highly conserved in the living kingdom. In humans, it has been found to be predominantly expressed in the thymus and in the brain. CYP2U1 is considered as an "orphan" enzyme as few data are available on its physiological function(s) and active site topology. Its only subs...
Receptor activator of nuclear factor-κB (RANK) and RANK ligand play a pivotal role in bone metabolism, and selective targeting of RANK signaling has become a promising therapeutic strategy in the management of resorptive bone diseases. Existing antibody-based therapies and novel inhibitors currently in development were designed to target the ligand...
Kidney International aims to inform the renal researcher and practicing nephrologists on all aspects of renal research. Clinical and basic renal research, commentaries, The Renal Consult, Nephrology sans Frontieres, minireviews, reviews, Nephrology Images, Journal Club. Published weekly online and twice a month in print.
Background. 1H-NMR is a non-biased technique for the quantification of small molecules that could result in the identification and characterization of potential biomarkers with prognostic value and contribute to better understand pathophysiology of diseases. Methods. In this study, we used 1H-NMR spectroscopy to analyze the urinary metabolome of pa...
Tris(p-carboxyltetrathiaaryl)methyl (TAM) radicals, such as 1a ("Finland" radical), are useful EPR probes for oximetry. However they are rapidly metabolized by liver microsomes in the presence of NADPH, with formation of diamagnetic quinone-methide metabolites resulting from an oxidative decarboxylation of one of their carboxylate substituents. In...
An unknown impurity detected in small amounts during the heat treatment of artesunate-amodiaquine bilayer tablets was purified by semipreparative HPLC and identified by MS and NMR as the tetrahydrofuranyl acetate-rearranged derivative of anhydrodihydroartemisinin. When anhydrodihydroartemisinin was treated with a Fe(II) salt in acetonitrile-water s...
The anti-thrombotics of the tetrahydrothienopyridine series, clopidogrel and prasugrel, are prodrugs that must be metabolized in two steps to become pharmacologically active. The first step is the formation of a thiolactone metabolite. The second step is a cytochrome P450 (P450)-dependent oxidation of this thiolactone resulting in the formation of...
Evaluation of docking results is one of the most important problems for virtual screening and in silico drug design. Modern approaches for the identification of active compounds in a large data set of docked molecules use energy scoring functions. One of the general and most significant limitations of these methods relates to inaccurate binding ene...
ROC curves for the Coulomb contact set of protease. (A) Vectors were not filtered, (B) Vectors were filtered.
Notes: Different charges were tested for the contact search. ROC curves obtained using preliminary knowledge of the best leaf position in the tree and distances between the leaves in the tree.
ROC curves for the coulomb contact sets of protease (A and B) and thrombin (C and D). (A and C) Vectors were not filtered, (B and D) Vectors were filtered.
Notes: Different distances were tested for the contact search. ROC curves were obtained using preliminary knowledge of the best leaf position in the tree and distances between the leaves in the...
ROC curves for the selection 4 contact set of thrombin. (A) Vectors were not filtered, (B) Vectors were filtered.
Notes: Different distances were tested for the contact search. ROC curves were obtained using preliminary knowledge of the best leaf position in the tree and distances between the leaves in the tree.
Data for the selection 4 contact set of COX1. (A) Fingerprint before filtering, (B) Fingerprint after filtering, (C) ROC curves.
Note: ROC curves were obtained using preliminary knowledge of the best leaf position in the tree and distances between the leaves in the tree.
ROC curves for the AuPosSOM clustering and conventional scoring functions results.
Notes: ROC curves for AuPosSOM were obtained using preliminary knowledge of the best leaf position in the tree and distances between the leaves in the tree. ROC curves for the lipophilic contacts 2 selection is not shown as the results are close to those of lipophili...
AuPosSOM scoring.
Notes: ROC curves for ten runs of the AuPosSOM clustering. HB contact dataset. Filled circles: clustering without filtering, blank circles: clustering with filtering.
AuPosSOM scoring.
Notes: ROC curves for ten runs of the AuPosSOM clustering. Coulomb contact dataset. Filled circles: clustering without filtering, blank circles: clustering with filtering.
IFN-γ is a master regulator of the immune responses that occur in the transplanted kidney, acting both on the immune system and on the graft itself. The cellular responses to IFN-γ are complex, and emerging evidence suggests that IFN-γ may regulate autophagic functions. Conversely, autophagy modulates innate and adaptive immune functions in various...
The transcription factor NF-E2-related factor 2 (Nrf2) is a master regulator of a genetic program, termed the phase 2 response, that controls redox homeostasis and participates in multiple aspects of physiology and pathology. Nrf2 protein stability is regulated by two E3 ubiquitin ligase adaptors, Keap1 and β-TrCP, the latter of which was only rece...
Clopidogrel, a widely used antithrombotic (PlavixTm), is actually a prodrug that requires a two step enzymatic conversion to an active metabolite (a N subtituted (Z) 3-carboxymethylidene 4-mercapto-piperidine).
For Clopidogrel the first step is the P450-mediated mono-oxygenation of the thiophene ring, yielding a thiolactone, 2-oxo-clopidogrel (2-...
The mechanism generally admitted for the bioactivation of the antithrombotic prodrug, prasugrel, 1c, is its two-step enzymatic conversion into a biologically active thiol metabolite. The first step is an esterase-catalyzed hydrolysis of its acetate function leading to a thiolactone metabolite 2c. The second step was described as a cytochrome P450 (...
The scope of the biotransformation of a series of azaarene compounds by recombinant whole-cells of Escherichia coli JM109(DE3)(pDTG141) expressing the naphthalene dioxygenase system (NDOS) from Pseudomonas sp. NCIB 9616-4 was explored. The present study establishes that several bicyclic azaarenes are good substrates in the NDO-catalysed reaction, g...
The mechanism generally admitted for the bioactivation of the antithrombotic prodrug, clopidogrel, is its two-step enzymatic conversion into a biologically active thiol metabolite. The first step is a classical cytochrome P450 (P450)-dependent monooxygenation of its thiophene ring leading to 2-oxo-clopidogrel, a thiolactone metabolite. The second s...
Docking techniques on therapeutic targets are widely used for the investigation of the protein-ligand interaction and virtual screening. The very important problem is to distinguish biologically active compounds from inactive ones in the large set of the docked molecules. AuPosSOM is a new software for the evaluation of the docking results. The app...
In the absence of crystallographic data, NMR has emerged as the best way to define protein-ligand interactions. Using NMR experiments based on magnetization transfer, one can sort bound from unbound molecules, estimate the dissociation constant, identify contacts implied in the binding, characterize the structure of the bound ligand and conduct lig...
ABSTRACT :. We have shown in the past that the thiophene ring can bemetabolized trough two primary cytochrome P450 catalyzed oxidation pathways :C-hydroxylation leading to a 2-hydroxy-thiophene (tautomeric a thiolactone) andS-oxidation leading to thiophene-S-oxides which are generally unstable anddimerize through Diels Alder cycloaddition. In prese...
Metabolic activation of the tetrahydro-thienopyridine antithrombotic prodrug, prasugrel, involves two steps: an esterase-dependent hydrolysis of its acetate function leading to thiolactone 6 and a cytochrome P450 (P450)-catalyzed oxidative cleavage of this thiolactone. This article shows that this second step involves the intermediate formation of...
Scoring functions provided by the docking software are still a major limiting factor in virtual screening (VS) process to classify compounds. Score analysis of the docking is not able to find out all active compounds. This is due to a bad estimation of the ligand binding energies. Making the assumption that active compounds should have specific con...
The synthesis of new enantiopure polyfunctionalised diazepanone scaffolds is described. The key steps involve the opening of an azido-epoxide C4 building block derived from L-ascorbic or D-isoascorbic acid by a L-serine derivative followed by a lactonisation-lactamisation two-step sequence.
23s0 J. Chem. lnf. Model. 2O08, 48,2350 2361
Structure of the Complex between Phophorylated Subrates and the SCF Beta-TrcP Ubiquitin Ligase Receptor A Combined NMR, Molecular Modeling, and Dockirg Approach
Nathalie Evrard-Todeschi,t Julien Pons,t Josyane Gharbi-Benarous,t Gildas Bertho,t , Richard Benarous,i and Jean-Pierre Girault*'t
t Laboratoire...
Tris-(p-carboxyltetrathiaaryl)methyl radical EPR probes are very efficiently oxidized by superoxide and alkylperoxyl radicals with selective formation of quinone-methide products; this should explain the previously reported specific measurement of O2*- using these EPR probes.
Metabolic cleavage of the CO-S bond of some thioesters RCOSR' with the formation of RCOOH requires a monooxygenase-dependent oxidative activation of this bond. The nature of the S-containing product(s) resulting from this cleavage remains unclear in most cases. This communication provides the first evidence for the formation of sulfenic acid interm...
The binding of phosphorylated peptides to the receptor plays a major role in many basic cellular processes in a variety of pathological states. Human beta-TrCP is a key component of a recently characterized E3 ubiquitin ligase complex that regulates protein degradation through the ubiquitin-dependent proteasome pathway. Docking studies were carried...
Prion protein is a strongly conserved and ubiquitous glycoprotein. The conformational conversion of the non-pathogenic cellular prion isoform (PrP(C)) into a pathogenic scrapie isoform (PrP(Sc)) is a fundamental event in the onset of transmissible spongiform encephalopathies (TSE). During this conversion, helix H1 and its two flanking loops are kno...
Easily obtained cyclic 6,7-dehydro-L-lysine was employed as starting template to generate variously substituted enantiopure 3-aminocaprolactams. syn-Dihydroxylation, hydroxymethoxylation, halomethoxylation and subsequent eliminations were performed with this starting enelactam, thus leading, in regio- and stereoselective manners, to new mono-,di- a...
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ATF4 plays a crucial role in the cellular response to stress. The E3 ubiquitin ligase, SCF beta-TrCP protein responsible for ATF4 degradation by the proteasome, binds to ATF4 through a DpSGXXXpS phosphorylation motif, which is similar but not identical to the DpSGXXpS motif found in most other substrates of beta-TrCP. NMR studies were performed on...
ATF4 plays a crucial role in the cellular response to stress and the F-box protein beta-TrCP, the receptor component of the SCF E3 ubiquitin ligase responsible for ATF4 degradation by the proteasome, binds to ATF4, and controls its stability. Association between the two proteins depends on ATF4 phosphorylation of serine residues 219 and 224 present...
The synthesis of polyfunctionalised enantiopure 1,4-diazepan-3-one scaffolds from L-serine derivatives and azidoepoxides readily available from either L-ascorbic or D-isoascorbic acid, allowing access to various configurations at chiral centres, is described. The key steps are the nucleophilic opening of the epoxide by the amine of serine followed...
Fronds of the fern Microsorum scolopendria are widely used in traditional medicine in the Society Islands. They were investigated for the presence of ecdysteroids, which might be responsible for at least some of their medicinal properties. M. scolopendria represents an excellent source of ecdysone (0.16% of dry weight) and 20-hydroxyecdysone (0.20%...
The IkappaB-alpha protein, inhibitor of the transcription factor nuclear factor-kappaB (NF-kappaB), is a cellular substrate of beta-transducin repeat containing protein (beta-TrCP). beta-TrCP is the F-box protein component of an Skp1/Cul1/F-box (SCF)-type ubiquitin ligase complex. beta-TrCP targets the protein IkappaB-alpha for ubiquitination, foll...
Molecular recognition by calix[6]arene-based receptors bearing three primary alkylamino side chain arms (1) is described. Complexation of ZnII ion provides the dinuclear μ-hydroxo complex , XRD characterization of which, together with solution studies, provided evidence of its hosting of neutral polar organic guests G. Treatment of this complex wit...
The interaction of the P-beta-Cat(19-44) peptide, a 26 amino acid peptide (K(19)AAVSHWQQQSYLDpSGIHpSGATTTAP(44)) that mimics the phosphorylated beta-Catenin antigen, has been studied with its monoclonal antibody BC-22, by transferred nuclear Overhauser effect NMR spectroscopy (TRNOESY) and saturation transfer difference NMR (STD NMR) spectroscopy....
The bulky, asymmetric analog of the antitumor drug cisplatin, [PtCl(2)(tmen)] (tmen = N,N,N'-trimethylethylenediamine), was used to produce crosslinks with the dinucleotide d(GpG), modeling the most frequent lesions that cisplatin and its analogs cause to DNA. The ligand tmen was chosen because it is expected to constrain the guanine cis to the NMe...
Questions
Question (1)
We all knows that metabolomics by NMR is a very promising technic for human health as seen in the many scientific publications. Phenome centers are using NMR technics for metabolic profiling using biofluids, but i am wondering how this information is used to give back real benefits to patients ? Do you know if there is already somewhere in the world a concrete example of NMR-based metabolomics application or an everyday application in the human health domain ?
