12 results on '"Balkis Eddhif"'
Search Results
2. Primary Step Towards In Situ Detection of Chemical Biomarkers in the UNIVERSE via Liquid-Based Analytical System: Development of an Automated Online Trapping/Liquid Chromatography System
- Author
-
Thomas Ribette, Bertrand Leroux, Balkis Eddhif, Audrey Allavena, Marc David, Robert Sternberg, Pauline Poinot, and Claude Geffroy-Rodier
- Subjects
space instrumentation ,liquid chromatography ,oligopeptides ,trapping system ,Organic chemistry ,QD241-441 - Abstract
The search for biomarkers in our solar system is a fundamental challenge for the space research community. It encompasses major difficulties linked to their very low concentration levels, their ambiguous origins (biotic or abiotic), as well as their diversity and complexity. Even if, in 40 years’ time, great improvements in sample pre-treatment, chromatographic separation and mass spectrometry detection have been achieved, there is still a need for new in situ scientific instrumentation. This work presents an original liquid chromatographic system with a trapping unit dedicated to the one-pot detection of a large set of non-volatile extra-terrestrial compounds. It is composed of two units, monitored by a single pump. The first unit is an online trapping unit able to trap polar, apolar, monomeric and polymeric organics. The second unit is an online analytical unit with a high-resolution Q-Orbitrap mass spectrometer. The designed single pump system was as efficient as a laboratory dual-trap LC system for the analysis of amino acids, nucleobases and oligopeptides. The overall setup significantly improves sensitivity, providing limits of detection ranging from ppb to ppt levels, thus meeting with in situ enquiries.
- Published
- 2019
- Full Text
- View/download PDF
3. Evidence for Proteogenic Peptide-like Sequences in Meteorites Through an Enzyme-Catalysed Stereoselective Hydrolysis Strategy
- Author
-
Justin Lange, Louis Le Sergeant d'Hendecourt, Quentin Blancart Remaury, Balkis Eddhif, Sébastien Papot, Fabiola Djago, Claude Geffroy Rodier, Pauline Poinot, Alexander Ruf, Nathalie Karpel Vel Leitner, and Grégoire Danger
- Subjects
chemistry.chemical_classification ,Murchison meteorite ,Hydrolysis ,Meteorite ,chemistry ,Stereochemistry ,Enzymatic hydrolysis ,Acid hydrolysis ,Peptide ,Peptide sequence ,Amino acid - Abstract
In this manuscript, we evidenced for the first time proteogenic like peptide sequences in meteorite thanks to an original stereoselective enzymatic hydrolysis. Within this framework, we have first characterised the amino acids content of two meteorites, Murchison and Allende, after the standard acid hydrolysis protocol currently used in astronomical studies. To reach this goal, we have developed a highly sensitive chiral LC-MS method and we have highlighted new l- and d-enantiomers, never detected before in both meteorites. These primary findings extend the list of amino acids already found in meteorites. We next investigated the presence of proteogenic like peptide sequences. For that, we have compared the amounts of amino acids l- and d-enantiomers released from either the standard acid hydrolysis or our stereoselective peptidase hydrolysis. Thanks to this strategy, we have highlighted the presence of peptide sequences involving proteogenic l-amino acids in the Murchison together with their absence in Allende, which is consistent with the respective organic content of both meteorites. Furthermore, we demonstrated that the peptide sequences were indigenous to the Murchison meteorite.
- Published
- 2020
4. A Novel Proteomics-Based Strategy for the Investigation of Peptide Sequences in Extraterrestrial Samples
- Author
-
Pauline Poinot, Quentin Blancart Remaury, Justin Lange, Alexander Ruf, Louis L S Hendecourt, Grégoire Danger, Nathalie Karpel Vel Leitner, Claude Geffroy Rodier, Sébastien Papot, Fabiola Djago, Balkis Eddhif, Institut de Chimie des Milieux et Matériaux de Poitiers (IC2MP), Université de Poitiers-Institut national des sciences de l'Univers (INSU - CNRS)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Physique des interactions ioniques et moléculaires (PIIM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), and ANR-16-CE29-0015,RAHIIA_SSOM,Analyses de résidus provenant d'analogues de glace interstellaire pour la compréhension de la formation de la matière organique du Système Solaire(2016)
- Subjects
Proteomics ,0301 basic medicine ,chemistry.chemical_classification ,Extraterrestrial Environment ,030102 biochemistry & molecular biology ,Computer science ,Peptide ,Context (language use) ,Meteoroids ,General Chemistry ,Computational biology ,Biochemistry ,Method development ,03 medical and health sciences ,030104 developmental biology ,chemistry ,Tandem Mass Spectrometry ,Proof of concept ,Extraterrestrial life ,Peptide bond ,Peptides ,[SDU.ENVI]Sciences of the Universe [physics]/Continental interfaces, environment ,Chromatography, Liquid - Abstract
International audience; Method development is part of the objectives of astrophysical community for characterizing the organic matter in objects of the Solar System. In this context, we report on the development of an enzyme-catalyzed stereoselective hydrolysis, inspired from the proteomics discipline, which has enabled the indirect detection of peptide sequences in extraterrestrial samples. A proof of concept has been performed on a Murchison extract. We showed that our approach can successfully highlight L- and D-amino acids involved in peptide bonds. While we showed that some D-amino acids must have been involved in peptide bonds, we cannot at this stage conclude on the indigenous or exogenous nature of these biopolymers. However, our strategy constitutes the first step towards the direct UPLC-MS evidence of peptide sequences in extraterrestrial samples. It should thus participate to deepen knowledge on the molecules available in the Solar System, hence providing new clues on their chemical history, especially on Earth.
- Published
- 2020
5. The Challenging Detection of Nucleobases from Pre-accretional Astrophysical Ice Analogs
- Author
-
Alexander Ruf, Grégoire Danger, Louis Le Sergeant d'Hendecourt, Justin Lange, Pauline Poinot, Claude Geffroy, Balkis Eddhif, Physique des interactions ioniques et moléculaires (PIIM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie des Milieux et Matériaux de Poitiers (IC2MP), Université de Poitiers-Institut national des sciences de l'Univers (INSU - CNRS)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), ANR-16-CE29-0015,RAHIIA_SSOM,Analyses de résidus provenant d'analogues de glace interstellaire pour la compréhension de la formation de la matière organique du Système Solaire(2016), and Aix Marseille Université (AMU)
- Subjects
Planetesimal ,Astrochemistry ,010504 meteorology & atmospheric sciences ,[SDU.ASTR.EP]Sciences of the Universe [physics]/Astrophysics [astro-ph]/Earth and Planetary Astrophysics [astro-ph.EP] ,01 natural sciences ,Astrobiology ,Nucleobase ,Pre-biotic astrochemistry ,0103 physical sciences ,[CHIM]Chemical Sciences ,010303 astronomy & astrophysics ,ComputingMilieux_MISCELLANEOUS ,0105 earth and related environmental sciences ,Physics ,chemistry.chemical_classification ,[PHYS]Physics [physics] ,Ice formation ,Molecular cloud ,Astronomy and Astrophysics ,Early Earth ,Accretion (astrophysics) ,Amino acid ,Meteorite ,chemistry ,13. Climate action ,Space and Planetary Science - Abstract
International audience; Amino acids, sugars, and nucleobases are considered as the so-called molecular bricks of life, the major subunits of proteins and genetic materials. All three chemical families have been previously detected in meteorites. In dense molecular cloud ice analogs, the formation of a large set of amino acids and sugars (+derivatives) has been observed. In this contribution, we demonstrate that similar ices (H2O:13CH3OH:NH3 ices, 2:1:1) can also lead to the formation of nucleobases. Using combined UPLC-Orbitrap mass spectrometric and UPLC-SRM-triple quadrupole mass spectrometric analyses, we have unambiguously detected cytosine in these primitive, realistic astrophysical ice analogs. Additionally, a huge variety of nucleobase isomers was observed. These results indicate that all central subunits of biochemical materials may have already been present at early stages of chemical evolution of the protosolar nebula, before accretion toward planetesimals. Consequently, the formation of amino acids, sugars, and nucleobases does not necessarily require secondary alteration processes inside meteoritic parent bodies. They might have been supplied from dense molecular cloud ices toward post-accretional objects, such as nonaqueously modified comets, and subsequently delivered onto the early Earth's surface, potentially triggering the emergence of prebiotic chemistry leading to the first living systems.
- Published
- 2019
6. TCA precipitation and ethanol/HCl single-step purification evaluation: One-dimensional gel electrophoresis, bradford assays, spectrofluorometry and Raman spectroscopy data on HSA, Rnase, lysozyme - Mascots and Skyline data
- Author
-
Sébastien Papot, Balkis Eddhif, Claude Geffroy-Rodier, Nadia Guignard, Yann Batonneau, Pauline Poinot, Jonathan Clarhaut, Institut de Chimie des Milieux et Matériaux de Poitiers (IC2MP), Université de Poitiers-Institut national des sciences de l'Univers (INSU - CNRS)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de physiologie et biologie cellulaires (IPBC), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), and Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)
- Subjects
0301 basic medicine ,RNase P ,Cellulase ,lcsh:Computer applications to medicine. Medical informatics ,01 natural sciences ,03 medical and health sciences ,chemistry.chemical_compound ,symbols.namesake ,Ribonuclease ,lcsh:Science (General) ,ComputingMilieux_MISCELLANEOUS ,Proteomics and Biochemistry ,Gel electrophoresis ,Multidisciplinary ,Ethanol ,Chromatography ,biology ,010401 analytical chemistry ,[CHIM.CATA]Chemical Sciences/Catalysis ,6. Clean water ,Molten globule ,0104 chemical sciences ,030104 developmental biology ,chemistry ,biology.protein ,symbols ,lcsh:R858-859.7 ,Lysozyme ,Raman spectroscopy ,lcsh:Q1-390 - Abstract
The data presented here are related to the research paper entitled “Study of a Novel Agent for TCA Precipitated Proteins Washing - Comprehensive Insights into the Role of Ethanol/HCl on Molten Globule State by Multi-Spectroscopic Analyses” (Eddhif et al., submitted for publication) [1]. The suitability of ethanol/HCl for the washing of TCA-precipitated proteins was first investigated on standard solution of HSA, cellulase, ribonuclease and lysozyme. Recoveries were assessed by one-dimensional gel electrophoresis, Bradford assays and UPLC-HRMS. The mechanistic that triggers protein conformational changes at each purification stage was then investigated by Raman spectroscopy and spectrofluorometry. Finally, the efficiency of the method was evaluated on three different complex samples (mouse liver, river biofilm, loamy soil surface). Proteins profiling was assessed by gel electrophoresis and by UPLC-HRMS.
- Published
- 2018
7. Study of a novel agent for TCA precipitated proteins washing - comprehensive insights into the role of ethanol/HCl on molten globule state by multi-spectroscopic analyses
- Author
-
Nadia Guignard, Yann Batonneau, Pauline Poinot, Justin Lange, Sébastien Papot, Jonathan Clarhaut, Claude Geffroy-Rodier, Balkis Eddhif, Institut de Chimie des Milieux et Matériaux de Poitiers (IC2MP), Université de Poitiers-Institut national des sciences de l'Univers (INSU - CNRS)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de catalyse en chimie organique (LACCO), Université de Poitiers-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), INSERM CIC 0802 (INSERM - CHU de Poitiers), and Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
Proteomics ,0301 basic medicine ,Biophysics ,Biochemistry ,Specimen Handling ,03 medical and health sciences ,chemistry.chemical_compound ,Protein purification ,Methods ,Acetone ,[CHIM]Chemical Sciences ,Animals ,Chemical Precipitation ,Protein precipitation ,Trichloroacetic Acid ,ComputingMilieux_MISCELLANEOUS ,Chromatography ,Aqueous solution ,Ethanol ,Proteolytic enzymes ,Proteins ,Molten globule ,Solvent ,030104 developmental biology ,Solubility ,chemistry ,Reagent ,Hydrochloric Acid - Abstract
Sample preparation for mass spectrometry-based proteomics is a key step for ensuring reliable data. In gel-free experimental workflows, protein purification often starts with a precipitation stage using trichloroacetic acid (TCA). In presence of TCA, proteins precipitate in a stable molten globule state making the pellet difficult to solubilize in aqueous buffer for proteolytic digestion and MS analysis. In this context, the objective of this work was to study the suitability of a novel agent, ethanol/HCl, for the washing of TCA-precipitated proteins. This method optimized the recovery of proteins in aqueous buffer (50 to 96%) while current organic solvents led to losses of material. Following a mechanistic study, the effect of ethanol/HCl on the conformation of TCA-precipitated proteins was investigated. It was shown that the reagent triggered the unfolding of TCA-stabilized molten globule into a reversible intermediate, characterized by a specific Raman signature, which favored protein subsequent resolubilization. Finally, the efficiency of ethanol/HCl for the washing of TCA-precipitated proteins extracted from a biofilm, a soil or a mouse liver was demonstrated (data available via ProteomeXchange with identifier PXD008110 ). Being versatile and simple, it could be of great interest to include an ethanol/HCl wash-step to produce high-quality protein extracts. Significance In mass spectrometry-based proteomics workflows, proteins precipitation and/or washing usually involves the use of acetone. In fact, this solvent is effective for removing both biological interferences (e.g. lipids) and chemicals employed in protein extraction/purification protocols (e.g. TCA, SDS). However, the use of acetone can lead to significant protein losses. Moreover, when proteins are precipitated with TCA, the acetone-treated precipitate remains hard to disperse, leading to poor resolubilization of proteins in aqueous buffers. Here, we investigated the use of ethanol/HCl for washing TCA-precipitated proteins, with the aim to produce high-quality protein extracts which can be directly analyzed by LC-MS. An opening study on standard solutions showed that ethanol/HCl led to reduced losses of proteins compared to usual solvents (i.e. acetone and ethanol). This reagent also enabled a better solubilization of proteins in aqueous buffer that is necessary for their direct trypsin digestion and LC-HRMS analysis. A mechanistic study, performed through several spectroscopic analyses (LC-HRMS, Raman, spectrofluorometry), showed that treatment with ethanol/HCl induced conformational changes of TCA-precipitated proteins. Finally, we compared the efficiency of ethanol/HCl to published protocols for the washing of protein extracts from three different complex samples (i.e. soil, biofilm, and mouse liver). Our results demonstrated that ethanol/HCl is a valuable alternative to previous protein washing methods and, therefore could become a useful tool in mass spectrometry-based proteomics workflows for various applications (e.g. clinical research, chemical biology, environmental metaproteomics…).
- Published
- 2018
8. Primary Step Towards In Situ Detection of Chemical Biomarkers in the UNIVERSE via Liquid-Based Analytical System: Development of an Automated Online Trapping/Liquid Chromatography System
- Author
-
Claude Geffroy-Rodier, Pauline Poinot, Audrey Allavena, Bertrand Leroux, Balkis Eddhif, Marc David, Robert Sternberg, and Thomas Ribette
- Subjects
In situ ,Materials science ,Pharmaceutical Science ,Trapping ,Mass spectrometry ,01 natural sciences ,Article ,Analytical Chemistry ,Trap (computing) ,lcsh:QD241-441 ,lcsh:Organic chemistry ,Tandem Mass Spectrometry ,0103 physical sciences ,Drug Discovery ,Humans ,liquid chromatography ,Sensitivity (control systems) ,Physical and Theoretical Chemistry ,Amino Acids ,Organic Chemicals ,010303 astronomy & astrophysics ,Detection limit ,Chromatography ,010401 analytical chemistry ,Organic Chemistry ,Ranging ,0104 chemical sciences ,space instrumentation ,Chemistry (miscellaneous) ,trapping system ,Molecular Medicine ,Polar ,Solar System ,oligopeptides ,Biomarkers ,Chromatography, Liquid - Abstract
The search for biomarkers in our solar system is a fundamental challenge for the space research community. It encompasses major difficulties linked to their very low concentration levels, their ambiguous origins (biotic or abiotic), as well as their diversity and complexity. Even if, in 40 years&rsquo, time, great improvements in sample pre-treatment, chromatographic separation and mass spectrometry detection have been achieved, there is still a need for new in situ scientific instrumentation. This work presents an original liquid chromatographic system with a trapping unit dedicated to the one-pot detection of a large set of non-volatile extra-terrestrial compounds. It is composed of two units, monitored by a single pump. The first unit is an online trapping unit able to trap polar, apolar, monomeric and polymeric organics. The second unit is an online analytical unit with a high-resolution Q-Orbitrap mass spectrometer. The designed single pump system was as efficient as a laboratory dual-trap LC system for the analysis of amino acids, nucleobases and oligopeptides. The overall setup significantly improves sensitivity, providing limits of detection ranging from ppb to ppt levels, thus meeting with in situ enquiries.
- Published
- 2019
9. Controlled Release of a Micelle Payload via Sequential Enzymatic and Bioorthogonal Reactions in Living Systems
- Author
-
Pauline Poinot, Sébastien Papot, Karine Porte, Eric Doris, Edmond Gravel, Anne Wijkhuisen, Jonathan Clarhaut, Elodie Péraudeau, Frédéric Taran, Brigitte Renoux, Balkis Eddhif, Davide Audisio, Service de Chimie Bio-Organique et de Marquage (SCBM), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Chimie des Milieux et Matériaux de Poitiers (IC2MP), Université de Poitiers-Institut national des sciences de l'Univers (INSU - CNRS)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut de physiologie et biologie cellulaires (IPBC), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Laboratoire d'Ingénierie des Anticorps pour la Santé (LIAS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire de Marquage au Carbone 14 (LMC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Médicaments et Technologies pour la Santé (MTS), and École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)
- Subjects
Transplantation, Heterologous ,Tetrazoles ,Antineoplastic Agents ,010402 general chemistry ,Micelle ,01 natural sciences ,Catalysis ,Cyclooctanes ,Mice ,Glucuronides ,On demand ,Cell Line, Tumor ,Neoplasms ,Animals ,Humans ,ComputingMilieux_MISCELLANEOUS ,Micelles ,chemistry.chemical_classification ,Chemistry ,010405 organic chemistry ,Payload (computing) ,[CHIM.CATA]Chemical Sciences/Catalysis ,General Chemistry ,General Medicine ,Controlled release ,Combinatorial chemistry ,Living systems ,0104 chemical sciences ,Drug Liberation ,Kinetics ,Enzyme ,Pharmaceutical Preparations ,Alkynes ,Nanoparticles ,Click Chemistry ,Bioorthogonal chemistry - Abstract
A bioorthogonal approach is explored to release the content of nanoparticles on demand. Exploiting our recently described click-and-release technology, we developed a new generation of cleavable micelles able to disassemble through a sequential enzymatic and bioorthogonal activation process. Proof-of-concept experiments showed that this new approach could be successfully used to deliver the substances encapsulated into micelles in living cells as well as in mice by two complementary targeted strategies.
- Published
- 2019
10. A β-glucuronidase-responsive albumin-binding prodrug programmed for the double release of monomethyl auristatin E
- Author
-
Brigitte Renoux, Balkis Eddhif, Elodie Péraudeau, Laure Fangous, Pauline Poinot, Sébastien Papot, Camille Hötten, and Jonathan Clarhaut
- Subjects
Pharmacology ,chemistry.chemical_classification ,010405 organic chemistry ,Organic Chemistry ,Albumin ,Pharmaceutical Science ,Prodrug ,010402 general chemistry ,01 natural sciences ,Biochemistry ,In vitro ,0104 chemical sciences ,Glucuronidase ,chemistry.chemical_compound ,Chemistry ,Enzyme ,Monomethyl auristatin E ,chemistry ,In vivo ,Drug Discovery ,Molecular Medicine ,Colorectal adenocarcinoma - Abstract
We report on the synthesis, in vitro and in vivo biological evaluations of a dimeric β-glucuronidase-responsive albumin-binding prodrug designed for the double release of MMAE upon a single enzymatic activation step. This prodrug produced a significant antitumour activity in mice bearing subcutaneous LS174T colorectal adenocarcinoma xenografts without inducing side effects.
- Published
- 2018
11. Development of liquid chromatography high resolution mass spectrometry strategies for the screening of complex organic matter: Application to astrophysical simulated materials
- Author
-
Robert Sternberg, Ninette Abou Mrad, Grégoire Danger, Balkis Eddhif, Thomas Ribette, Sylvie Liu, Audrey Allavena, Claude Geffroy-Rodier, Thierry Chiavassa, Pauline Poinot, Louis Le Sergeant d'Hendecourt, Aix Marseille Université (AMU), Institut de Chimie des Milieux et Matériaux de Poitiers (IC2MP), Université de Poitiers-Institut national des sciences de l'Univers (INSU - CNRS)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Physique des interactions ioniques et moléculaires (PIIM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Bioélectrochimie et Analyse du Milieu (LABAM), Université Paris-Est Marne-la-Vallée (UPEM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers-Institut de Chimie du CNRS (INC), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), and ANR-16-CE29-0015,RAHIIA_SSOM,Analyses de résidus provenant d'analogues de glace interstellaire pour la compréhension de la formation de la matière organique du Système Solaire(2016)
- Subjects
0301 basic medicine ,chemistry.chemical_classification ,Residue (complex analysis) ,Chromatography ,Analytical chemistry ,01 natural sciences ,Analytical Chemistry ,03 medical and health sciences ,030104 developmental biology ,chemistry ,[CHIM.ANAL]Chemical Sciences/Analytical chemistry ,0103 physical sciences ,High mass ,[CHIM]Chemical Sciences ,Organic matter ,Acid hydrolysis ,010303 astronomy & astrophysics ,ComputingMilieux_MISCELLANEOUS - Abstract
The present work aims at developing two LC-HRMS setups for the screening of organic matter in astrophysical samples. Their analytical development has been demonstrated on a 100-µg residue coming from the photo-thermo chemical processing of a cometary ice analog produced in laboratory. The first 1D-LC-HRMS setup combines a serially coupled columns configuration with HRMS detection. It has allowed to discriminate among different chemical families (amino acids, sugars, nucleobases and oligopeptides) in only one chromatographic run without neither a priori acid hydrolysis nor chemical derivatisation. The second setup is a dual-LC configuration which connects a series of trapping columns with analytical reverse-phase columns. By coupling on-line these two distinct LC units with a HRMS detection, high mass compounds (350
- Published
- 2018
12. Targeting the tumour microenvironment with an enzyme-responsive drug delivery system for the efficient therapy of breast and pancreatic cancers
- Author
-
Sébastien Papot, Balkis Eddhif, Alain Le Pape, Jérôme Alsarraf, Isabelle Tranoy-Opalinski, Brigitte Renoux, Thibaut Legigan, Pauline Poinot, Florian Raes, Elodie Péraudeau, Stéphanie Lerondel, Jonathan Clarhaut, Sergii Kolodych, Oleksandr Koniev, Institut de Chimie des Milieux et Matériaux de Poitiers (IC2MP), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers-Institut de Chimie du CNRS (INC), Transgenèse et archivage d'animaux modèles (TAAM), Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Conception et application de molécules bioactives (CAMB), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Transgénèse et Archivage d'Animaux Modèles - Centre d'Imagerie du Petit Animal (TAAM-CIPA), Institut de physiologie et biologie cellulaires (IPBC), and Université de Poitiers-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Drug ,Cancer chemotherapy ,media_common.quotation_subject ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Monomethylauristatin E ,Extracellular ,Medicine ,ComputingMilieux_MISCELLANEOUS ,media_common ,chemistry.chemical_classification ,business.industry ,Albumin ,General Chemistry ,[CHIM.CATA]Chemical Sciences/Catalysis ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,3. Good health ,Enzyme ,chemistry ,Immunology ,Drug delivery ,Cancer research ,0210 nano-technology ,business - Abstract
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, thereby enabling its passive accumulation in tumours where extracellular β-glucuronidase initiates the selective release of the drug. This targeting device produces outstanding therapeutic efficacy on orthotopic triple-negative mammary and pancreatic tumours in mice (50% and 33% of mice with the respective tumours cured), leading to impressive reduction or even disappearance of tumours without inducing side effects.
- Published
- 2017
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.