Mickaël Thomas, Jonathan Clarhaut, Pierre‐Olivier Strale, Isabelle Tranoy‐Opalinski, Joëlle Roche, Sébastien Papot,
... Search for more papers by this authorDr. Isabelle Tranoy-Opalinski, Dr. Isabelle Tranoy-Opalinski Laboratoire de Synthèse et Réactivité des Substances ... Search for more papers by this authorDr. Isabelle Tranoy-Opalinski, Dr. Isabelle Tranoy-Opalinski Laboratoire de Synthèse et Réactivité des Substances ...
Tópico(s): HIV/AIDS drug development and treatment
2011 - Wiley | ChemMedChem
John C. Fletcher, Kåre Berg, Knut Erik Tranøy,
... OsloSearch for more papers by this authorKnut Erik Tranøy Ph.D., Knut Erik Tranøy Ph.D. Professor of Philosophy, Institute of Philosophy, ... OsloSearch for more papers by this authorKnut Erik Tranøy Ph.D., Knut Erik Tranøy Ph.D. Professor of Philosophy, Institute of Philosophy, ...
Tópico(s): Ethics in medical practice
1985 - Wiley | Clinical Genetics
Brianne M. Collins, Henderikus J. Stam,
... countries, see Table 1.4 See, for example, Tranoy (Citation1996), Tranoy and Blomberg (Citation2005), and Ögren and Sandlund (Citation2007). ... see Huber (Citation1950), Cosyns-Duret (Citation1954), Adler (Citation1951), Tranoy and Blomberg (Citation2005), Robin (Citation1959), Wertheimer and Angel ( ... Lehoczky (Citation1951), Guerra and Sacco (Citation1954), Eringa (Citation1950), Tranoy and Blomberg (Citation2005), Furtado et al. (Citation1949), Barcia ...
Tópico(s): History of Medical Practice
2014 - Taylor & Francis | Journal of the History of the Neurosciences
Adrien Bessaguet, Quentin Blancart‐Remaury, Pauline Poinot, Isabelle Tranoy‐Opalinski, Sébastien Papot,
Rotaxanes and molecular knots exhibit particular properties resulting from the presence of a mechanical bond within their structure that maintains the molecular components interlocked in a permanent manner. On the other hand, the disassembly of the interlocked architecture through the breakdown of the mechanical bond can activate properties which are masked in the parent compound. Herein, we present the development of stimuli-responsive Cu
Tópico(s): Click Chemistry and Applications
2022 - Wiley | Angewandte Chemie International Edition
Noël Pairault, Adrien Bessaguet, Romain Barat, Lucas Frédéric, Grégory Pieters, Jeanne Crassous, Isabelle Tranoy‐Opalinski, Sébastien Papot,
Despite the impressive number of interlocked molecules described in the literature over the past 30 years, only a few stereoselective syntheses of mechanically chiral rotaxanes have been reported so far. In this study, we present the first diastereoselective synthesis of mechanically planar chiral [1]rotaxanes, that has been achieved using the active template Cu-mediated alkyne-azide cycloaddition reaction. This synthetic method has been applied to the preparation of a [1]rotaxane bearing a labile ...
Tópico(s): Luminescence and Fluorescent Materials
2020 - Royal Society of Chemistry | Chemical Science
Bent Sofus Tranøy, Mary Ann Stamsø, Ingrid Hjertaker,
Scandinavian countries are known for their universalistic welfare states, corporatist coordination, strong economic performances and egalitarian outcomes, an institutional combination often referred to as the 'Nordic model'. However, these countries also possess volatile and increasingly vulnerable housing markets characterised by periods of sharp increases in prices and rents and some of the highest debt to income ratios in the world. The combination of a universalistic welfare state and housing ...
Tópico(s): Economic Theory and Policy
2019 - Taylor & Francis | West European Politics
Mikaël Thomas, Jérôme Alsarraf, Nahla Araji, Isabelle Tranoy‐Opalinski, Brigitte Renoux, Sébastien Papot,
During more than a century, the Lossen rearrangement was supposed to occur exclusively in the presence of stochiometric amount of activating reagents. Very recently, it was demonstrated that the Lossen rearrangement can take place directly from free hydroxamic acids offering a renewal of interest for this reaction.
Tópico(s): Carbon dioxide utilization in catalysis
2019 - Royal Society of Chemistry | Organic & Biomolecular Chemistry
Herman Schwartz, Bent Sofus Tranøy,
How and why did comparative political economy (CPE) lose sight of the sources of growing macroeconomic and political instability, a problem that encompassed a growing financial bubble and then a crash in the housing market, a period of sluggish growth that plausibly constitutes secular stagnation, and a crisis of political legitimacy manifesting itself in the rise of antisystem “populist” parties? A gradual shift in CPE’s research agenda from macroeconomic to microeconomic concerns, and from demand- ...
Tópico(s): Economic Theory and Policy
2018 - SAGE Publishing | Politics & Society
Elodie Péraudeau, Laurent Cronier, Arnaud Monvoisin, Pauline Poinot, Coralie Mergault, François Guilhot, Isabelle Tranoy‐Opalinski, Brigitte Renoux, Sébastien Papot, Jonathan Clarhaut,
Several folate-drug conjugates are currently undergoing clinical trials for application in oncology. However, the efficacy of folate-targeted therapy strongly depends on the folate receptor (FR) abundance at the surface of cancer cells. Recently, it has been postulated that up-regulation of FRα by means of chemo-sensitizing agents could enhance the anticancer activity of FR-drug conjugates. In this study, we demonstrate in vitro that a combination of dexamethasone (Dexa) and valproic acid (VPA) increases ...
Tópico(s): Histone Deacetylase Inhibitors Research
2017 - Elsevier BV | Journal of Controlled Release
Brigitte Renoux, Florian Raes, Thibaut Legigan, Elodie Péraudeau, Balkis Eddhif, Pauline Poinot, Isabelle Tranoy‐Opalinski, Jérôme Alsarraf, Oleksandr Koniev, Sergii Kolodych, Stéphanie Lerondel, Alain Le Pape, Jonathan Clarhaut, Sébastien Papot,
The development of novel therapeutic strategies allowing the destruction of tumour cells while sparing healthy tissues is one of the main challenges of cancer chemotherapy. Here, we report on the design and antitumour activity of a low-molecular-weight drug delivery system programmed for the selective release of the potent monomethylauristatin E in the tumour microenvironment of solid tumours. After intravenous administration, this compound binds covalently to plasmatic albumin through Michael addition, ...
Tópico(s): Glycosylation and Glycoproteins Research
2017 - Royal Society of Chemistry | Chemical Science
Noël Pairault, Romain Barat, Isabelle Tranoy‐Opalinski, Brigitte Renoux, Mikaël Thomas, Sébastien Papot,
Recently, the development of rotaxane-based architectures for biological applications has started to attract interest. In this short review, we summarize the main advances that have been realized in this burgeoning area of research, including the design of squaraine-rotaxane dyes for optical bioimaging applications, host-rotaxanes as cellular transport agents, enzyme-responsive rotaxanes and mechanized mesoporous silica nanoparticles coated with “nanovalves” as drug delivery systems. Récemment, le ...
Tópico(s): Advanced biosensing and bioanalysis techniques
2016 - Elsevier BV | Comptes Rendus Chimie
Jérôme Alsarraf, Elodie Péraudeau, Pauline Poinot, Isabelle Tranoy‐Opalinski, Jonathan Clarhaut, Brigitte Renoux, Sébastien Papot,
We designed a dendritic folate–drug conjugate allowing the β-galactosidase-catalysed release of two MMAE molecules inside folate receptor-positive cancer cells.
Tópico(s): HIV/AIDS drug development and treatment
2015 - Royal Society of Chemistry | Chemical Communications
Romain Barat, Thibaut Legigan, Isabelle Tranoy‐Opalinski, Brigitte Renoux, Elodie Péraudeau, Jonathan Clarhaut, Pauline Poinot, Antony E. Fernandes, Vincent Aucagne, David A. Leigh, Sébastien Papot,
The development of mechanically interlocked molecular systems programmed to operate autonomously in biological environments is an emerging field of research with potential medicinal applications. Within this framework, functional rotaxane- and pseudorotaxane-based architectures are starting to attract interest for the delivery of anticancer drugs, with the ultimate goal to improve the efficiency of cancer chemotherapy. Here, we report an enzyme-sensitive [2]-rotaxane designed to release a potent ...
Tópico(s): Microtubule and mitosis dynamics
2015 - Royal Society of Chemistry | Chemical Science
Abstract Contractors in the oil and gas industry are experiencing an increased pressure to deliver projects at a lower cost and at a shorter schedule. Extensive requirements combined with strict governing documents restrict project designs. Therefore, contractors need efficient governing processes that capture customers' needs and ensure that system requirements relates to these customer needs. In the execution phase of a project, the engineering degrees of freedom are limited. In the early project ...
Tópico(s): Software Engineering Techniques and Practices
2014 - Wiley | INCOSE International Symposium
Isabelle Tranoy‐Opalinski, Thibaut Legigan, Romain Barat, Jonathan Clarhaut, Mikaël Thomas, Brigitte Renoux, Sébastien Papot,
The design of novel antitumor agents allowing the destruction of malignant cells while sparing healthy tissues is one of the major challenges in medicinal chemistry. In this context, the use of non-toxic prodrugs programmed to be selectively activated by beta-glucuronidase present at high concentration in the microenvironment of most solid tumors has attracted considerable attention. This review summarizes the major progresses that have been realized in this field over the past ten years. This includes ...
Tópico(s): Retinoids in leukemia and cellular processes
2014 - Elsevier BV | European Journal of Medicinal Chemistry
Jonathan Clarhaut, Sylvain Fraineau, Joëlle Guilhot, Elodie Péraudeau, Isabelle Tranoy‐Opalinski, Mikaël Thomas, Brigitte Renoux, Edouard Randriamalala, Patrick Bois, Aurélien Chatelier, Arnaud Monvoisin, Laurent Cronier, Sébastien Papot, François Guilhot,
Cytarabine combined with an anthracycline or an anthracenedione represents the usual intensive induction therapy for the treatment of AML. However, this protocol induces severe side effects and treatment-related mortality due to the lack of selectivity of these cytotoxic agents. In this paper, we present the study of the first galactosidase-responsive molecular "Trojan Horse" programmed for the delivery of doxorubicin exclusively inside AML blasts over-expressing the folate receptor (FR). This targeting ...
Tópico(s): Protein Degradation and Inhibitors
2013 - Elsevier BV | Leukemia Research
Thibaut Legigan, Jonathan Clarhaut, Brigitte Renoux, Isabelle Tranoy‐Opalinski, Arnaud Monvoisin, Christophe Jayle, Jérôme Alsarraf, Mikaël Thomas, Sébastien Papot,
We developed a glucuronide prodrug of the potent monomethylauristatin E (MMAE). This prodrug is significantly less toxic than the parent drug. However, in the presence of β-glucuronidase the prodrug leads to the efficient release of MMAE thereby triggering a subnanomolar cytotoxic activity against several cancer cell lines. Preliminary in vivo experiments conducted in C57BL/6 mice bearing a subcutaneous murine Lewis Lung Carcinoma (LLC) demonstrated the potential of this targeting system for the selective ...
Tópico(s): Proteoglycans and glycosaminoglycans research
2013 - Elsevier BV | European Journal of Medicinal Chemistry
Marion Grinda, Thibaut Legigan, Jonathan Clarhaut, Elodie Péraudeau, Isabelle Tranoy‐Opalinski, Brigitte Renoux, Mikaël Thomas, François Guilhot, Sébastien Papot,
The rise of chemical biology has led to the development of sophisticated molecular devices designed to explore and manipulate biological processes. Within this framework, we developed the first chemical system programmed for the selective internalization and subsequent enzyme-catalyzed double release of bioactive compounds inside a targeted population of cells. This system is composed of five distinct units including a targeting ligand, an enzymatic trigger, a self-immolative linker and two active ...
Tópico(s): Lipid Membrane Structure and Behavior
2013 - Royal Society of Chemistry | Organic & Biomolecular Chemistry
Thibaut Legigan, Jonathan Clarhaut, Isabelle Tranoy‐Opalinski, Arnaud Monvoisin, Brigitte Renoux, Mikaël Thomas, Alain Le Pape, Stéphanie Lerondel, Sébastien Papot,
Massive attack: Galactoside prodrugs have been designed that can be selectively activated by lysosomal β-galactosidase located inside cancer cells expressing a specific tumor-associated receptor. This efficient enzymatic process triggers a potent cytotoxic effect, releasing the potent antimitotic agent MMAE and allowing the destruction of both receptor-positive and surrounding receptor-negative tumor cells. Detailed facts of importance to specialist readers are published as "Supporting Information". ...
Tópico(s): Cellular transport and secretion
2012 - Wiley | Angewandte Chemie International Edition
Thibaut Legigan, Jonathan Clarhaut, Brigitte Renoux, Isabelle Tranoy‐Opalinski, Arnaud Monvoisin, Jean‐Marc Berjeaud, François Guilhot, Sébastien Papot,
In this paper we describe the synthesis and biological evaluation of the first β-glucuronidase-responsive albumin-binding prodrug designed for the selective delivery of doxorubicin at the tumor site. This prodrug leads to superior antitumor efficacy in mice compared to HMR 1826, a well-known glucuronide prodrug of doxorubicin that cannot bind covalently to circulating albumin. Furthermore, this compound inhibits tumor growth in a manner similar to that of doxorubicin while avoiding side effects ...
Tópico(s): Monoclonal and Polyclonal Antibodies Research
2012 - American Chemical Society | Journal of Medicinal Chemistry
Marion Grinda, Jonathan Clarhaut, Isabelle Tranoy‐Opalinski, Brigitte Renoux, Arnaud Monvoisin, Laurent Cronier, Sébastien Papot,
Amplified action! We developed the therapeutic first targeting system that includes a chemical amplifier programmed both to release two potent anticancer drugs after a single enzymatic activation step and become cytotoxic itself once the amplification process is completed. Detailed facts of importance to specialist readers are published as "Supporting Information". Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The ...
Tópico(s): Signaling Pathways in Disease
2011 - Wiley | ChemMedChem
Marion Grinda, Jonathan Clarhaut, Brigitte Renoux, Isabelle Tranoy‐Opalinski, Sébastien Papot,
The first self-immolative dendritic glucuronide prodrug of doxorubicin was studied with the aim to target β-glucuronidase overexpressed in the microenvironment of numerous tumors. This compound includes a chemical amplifier programmed to release two molecules of doxorubicin after a single enzymatic activation step. Upon β-glucuronidase activation, the dendritic prodrug was twice more toxic than its monomeric counterpart against H661 lung cancer cells.
Tópico(s): Glycosylation and Glycoproteins Research
2011 - Royal Society of Chemistry | MedChemComm
Isabelle Tranoy‐Opalinski, Antony E. Fernandes, Mikaël Thomas, J.-P. Gesson, Sébastien Papot,
The main drawback of most cancer chemotherapy is its relatively low ability to target tumour cells versus normal cells. As a consequence, chemotherapy is usually connected with severe side effects due to the toxicity of traditional cytostatic agents towards normal tissues. A few years ago, the site-specific activation of non-toxic prodrugs in tumours has been proposed in order to enhance the selectivity for the killing of cancer cells. Within this framework, most of the prodrugs that have been designed ...
Tópico(s): Click Chemistry and Applications
2008 - Bentham Science Publishers | Anti-Cancer Agents in Medicinal Chemistry
Isabelle Tranoy‐Opalinski, Antony E. Fernandes, Mikaël Thomas, Jean‐Pierre Gesson, Sébastien Papot,
The main drawback of most cancer chemotherapy is its relatively low ability to target tumour cells versus normal cells. As a consequence, chemotherapy is usually connected with severe side effects due to the toxicity of traditional cytostatic agents towards normal tissues. A few years ago, the site-specific activation of non-toxic prodrugs in tumours has been proposed in order to enhance the selectivity for the killing of cancer cells. Within this framework, most of the prodrugs that have been designed ...
Tópico(s): Click Chemistry and Applications
2008 - Bentham Science Publishers | Anti-Cancer Agents in Medicinal Chemistry
Mickaël Thomas, Jonathan Clarhaut, Isabelle Tranoy‐Opalinski, Jean‐Pierre Gesson, Joëlle Roche, Sébastien Papot,
Two glucuronide prodrugs of the histone deacetylase inhibitor CI-994 were synthesized. These compounds were found to be soluble in aqueous media and stable under physiological conditions. The carbamoyl derivatisation of CI-994 significantly decreased its toxicity towards NCI-H661 lung cancer cells. Prodrug incubation with β-glucuronidase in the culture media led efficiently to the release of the parent drug and thereby restoring its ability to decrease cell proliferation, to inhibit HDAC and to ...
Tópico(s): Epigenetics and DNA Methylation
2008 - Elsevier BV | Bioorganic & Medicinal Chemistry
Lynda Loudni, Joëlle Roche, Vincent Potiron, Jonathan Clarhaut, Christian Bachmann, Jean‐Pierre Gesson, Isabelle Tranoy‐Opalinski,
Tópico(s): Peptidase Inhibition and Analysis
2007 - Elsevier BV | Bioorganic & Medicinal Chemistry Letters
Mickaël Thomas, Freddy Rivault, Isabelle Tranoy‐Opalinski, Joëlle Roche, Jean‐Pierre Gesson, Sébastien Papot,
The β-O-glucuronide and β-O-galactoside of SAHA have been prepared and evaluated as prodrugs for selective cancer chemotherapy (ADEPT, PMT). These new compounds are stable under physiological conditions and do not exhibit any antiproliferative activity compared to the parent drug after a 48-h treatment of H661 cells. The glucuronide derivative did not lead to the release of the drug in the presence of either Escherichia coli or bovine liver β-glucuronidase. On the other hand, under enzymatic cleavage ...
Tópico(s): Inflammatory mediators and NSAID effects
2006 - Elsevier BV | Bioorganic & Medicinal Chemistry Letters
Lobotomy is still a hidden chapter in the history of Norwegian psychiatry. The main reasons, which are discussed here, may have been the role of Ørnulv Ødegård at Gaustad Hospital in Oslo and the links between health authorities and the power élite in Norwegian psychiatry.
Tópico(s): Neurology and Historical Studies
2005 - SAGE Publishing | History of Psychiatry
Sébastien Papot, Isabelle Tranoy, F Tillequin, Jean‐Claude Florent, J.‐P. GESSON,
Cancer chemotherapy is associated with severe side effects which may be reduced by selective liberation, at the tumour site, of a cytotoxic agent from a non-toxic prodrug. Several strategies are used to achieve the required selective activation : with enzymes which are present in higher concentration in, or close, to the tumour (β-glucuronidase, plasmin), with enzymes covalently linked to a macromolecular carrier able to recognize antigen positive cancer cells (ADEPT : Antibody Directed Enzyme Prodrug ...
Tópico(s): Biochemical and Molecular Research
2002 - Bentham Science Publishers | Current Medicinal Chemistry - Anti-Cancer Agents
Hariprasad Vankayalapati, Gurdial Singh, Isabelle Tranoy,
Glycosyl donors having a diphenylphosphinate and a propane-1,3-diyl phosphate leaving group were easily prepared by the addition of the anomeric hydroxyl group of 2,3,4,6-tetra-O-benzyl-α,β-d-glucopyranose to diphenylphosphinic and propane-1,3-diyldioxyphosphoryl chlorides. These glycosyl donors were selectively glycosylated with a number of primary and secondary oxygen nucleophiles in the presence of trimethylsilyl triflate (TMSOTf). The use of 1,3-diyl phosphate resulted in the stereoselective ...
Tópico(s): Enzyme Catalysis and Immobilization
2001 - Elsevier BV | Tetrahedron Asymmetry