8 results on '"Sergii Kolodych"'
Search Results
2. Non-specific interactions of antibody-oligonucleotide conjugates with living cells
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Victor Lehot, Isabelle Kuhn, Marc Nothisen, Stéphane Erb, Sergii Kolodych, Sarah Cianférani, Guilhem Chaubet, and Alain Wagner
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Medicine ,Science - Abstract
Abstract Antibody-Oligonucleotide Conjugates (AOCs) represent an emerging class of functionalized antibodies that have already been used in a wide variety of applications. While the impact of dye and drug conjugation on antibodies’ ability to bind their target has been extensively studied, little is known about the effect caused by the conjugation of hydrophilic and charged payloads such as oligonucleotides on the functions of an antibody. Previous observations of non-specific interactions of nucleic acids with untargeted cells prompted us to further investigate their impact on AOC binding abilities and cell selectivity. We synthesized a series of single- and double-stranded AOCs, as well as a human serum albumin-oligonucleotide conjugate, and studied their interactions with both targeted and non-targeted living cells using a time-resolved analysis of ligand binding assay. Our results indicate that conjugation of single strand oligonucleotides to proteins induce consistent non-specific interactions with cell surfaces while double strand oligonucleotides have little or no effect, depending on the preparation method.
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- 2021
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3. Automated linkage of proteins and payloads producing monodisperse conjugates
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Alexandre Hentz, Margaux Riomet, Sébastien Delacroix, Oleksandr Koniev, Anthony Ehkirch, Sylvain Ursuegui, Igor Dovgan, Steve Hessmann, Alain Wagner, Frédéric Taran, Sergii Kolodych, Sarah Cianférani, Conception et application de molécules bioactives (CAMB), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Syndivia SAS, Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), 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), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)
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Specific protein ,010405 organic chemistry ,Chemistry ,Dispersity ,Chemical modification ,Nanotechnology ,General Chemistry ,Linkage (mechanical) ,010402 general chemistry ,01 natural sciences ,0104 chemical sciences ,3. Good health ,law.invention ,law ,Surface modification ,[CHIM]Chemical Sciences ,Bioorthogonal chemistry ,Conjugate - Abstract
Controlled protein functionalization holds great promise for a wide variety of applications. However, despite intensive research, the stoichiometry of the functionalization reaction remains difficult to control due to the inherent stochasticity of the conjugation process. Classical approaches that exploit peculiar structural features of specific protein substrates, or introduce reactive handles via mutagenesis, are by essence limited in scope or require substantial protein reengineering. We herein present equimolar native chemical tagging (ENACT), which precisely controls the stoichiometry of inherently random conjugation reactions by combining iterative low-conversion chemical modification, process automation, and bioorthogonal trans-tagging. We discuss the broad applicability of this conjugation process to a variety of protein substrates and payloads., Controlled protein functionalization holds great promise for a wide variety of applications.
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- 2020
4. On the use of DNA as a linker in antibody-drug conjugates: synthesis, stability and in vitro potency
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Oleksandr Koniev, Sylvain Ursuegui, Igor Dovgan, Marc Nothisen, Manon Ripoll, Sergii Kolodych, Isabelle Kuhn, Alain Wagner, Sarah Cianférani, Alexandre Hentz, Anthony Ehkirch, Victor Lehot, Conception et application de molécules bioactives (CAMB), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Syndivia SAS, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)
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Immunoconjugates ,Aucun ,lcsh:Medicine ,Antineoplastic Agents ,010402 general chemistry ,01 natural sciences ,Article ,chemistry.chemical_compound ,Cell Line, Tumor ,[CHIM]Chemical Sciences ,Humans ,Cytotoxicity ,skin and connective tissue diseases ,lcsh:Science ,Multidisciplinary ,010405 organic chemistry ,Oligonucleotide ,lcsh:R ,hal-02870010 ,Proteins ,DNA ,Trastuzumab ,Ligand (biochemistry) ,In vitro ,3. Good health ,0104 chemical sciences ,body regions ,chemistry ,Monomethyl auristatin E ,Biochemistry ,Drug delivery ,lcsh:Q ,Oligopeptides ,Linker ,Chemical modification ,Conjugate - Abstract
Here we present the synthesis and evaluation of antibody-drug conjugates (ADCs), for which antibody and drug are non-covalently connected using complementary DNA linkers. These ADCs are composed of trastuzumab, an antibody targeting HER2 receptors overexpressed on breast cancer cells, and monomethyl auristatin E (MMAE) as a drug payload. In this new ADC format, trastuzumab conjugated to a 37-mer oligonucleotide (ON) was prepared and hybridized with its complementary ON modified at 5-end with MMAE (cON-MMAE) in order to obtain trastuzumab-DNA-MMAE. As an advantage, the cON-MMAE was completely soluble in water, which decreases overall hydrophobicity of toxic payload, an important characteristic of ADCs. The stability in the human plasma of these non-engineered ON-based linkers was investigated and showed a satisfactory half-life of 5.8 days for the trastuzumab-DNA format. Finally, we investigated the in vitro cytotoxicity profile of both the DNA-linked ADC and the ON-drug conjugates and compared them with classical covalently linked ADC. Interestingly, we found increased cytotoxicity for MMAE compared to cON-MMAE and an EC50 in the nanomolar range for trastuzumab-DNA-MMAE on HER2-positive cells. Although this proved to be less potent than classically linked ADC with picomolar range EC50, the difference in cytotoxicity between naked payload and conjugated payload was significant when an ON linker was used. We also observed an interesting increase in cytotoxicity of trastuzumab-DNA-MMAE on HER2-negative cells. This was attributed to enhanced non-specific interaction triggered by the DNA strand as it could be confirmed using ligand tracer assay.
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- 2020
5. Development and evaluation of β-galactosidase-sensitive antibody-drug conjugates
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Oleksandr Koniev, Sergii Kolodych, Christian D. Muller, Brigitte Renoux, Sébastien Papot, Alain Wagner, Pauline Poinot, Wojciech Krezel, Jitka Eberova, Chloé Michel, Anthony Ehkirch, Sébastien Delacroix, Sarah Cianférani, Laboratoire de Biomécanique et Mécanique des Chocs (LBMC UMR T9406), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR), Conception et application de molécules bioactives (CAMB), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Spectrométrie de Masse BioOrganique [Strasbourg] (LSMBO), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), 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), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Institut Pluridisciplinaire Hubert Curien (IPHC), and Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)
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Drug ,Antibody-drug conjugate ,Immunoconjugates ,media_common.quotation_subject ,Mice, Nude ,Breast Neoplasms ,Pharmacology ,010402 general chemistry ,Ado-Trastuzumab Emtansine ,01 natural sciences ,chemistry.chemical_compound ,Antineoplastic Agents, Immunological ,Trastuzumab ,Cell Line, Tumor ,Drug Discovery ,medicine ,Animals ,Humans ,[CHIM]Chemical Sciences ,Maytansine ,ComputingMilieux_MISCELLANEOUS ,media_common ,Cell Proliferation ,010405 organic chemistry ,[CHIM.ORGA]Chemical Sciences/Organic chemistry ,Organic Chemistry ,Cancer ,General Medicine ,medicine.disease ,beta-Galactosidase ,Galactoside ,0104 chemical sciences ,3. Good health ,Carcinoma, Ductal ,Monomethyl auristatin E ,chemistry ,Trastuzumab emtansine ,Drug delivery ,Female ,medicine.drug - Abstract
The selective destruction of tumour cells while sparing healthy tissues is one of the main challenges in cancer therapy. Antibody-drug conjugates (ADCs) are arguably the most rapidly expanding class of targeted cancer therapies. Efficient drug conjugation and release technologies are essential for the development of these new therapeutic agents. In response to the ever-increasing demand for efficient drug release systems, we have developed a new class of β-galactosidase-cleavable linkers for ADCs. Within this framework, novel payloads comprising a galactoside linker, the monomethyl auristatin E (MMAE) and cysteine-reactive groups were synthesized, conjugated with trastuzumab and evaluated both in vitro and in vivo. The ADCs with galactoside linkers demonstrated superior therapeutic efficacy in mice compared to the marketed trastuzumab emtansine used for the treatment of breast cancer.
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- 2017
6. Targeting the tumour microenvironment with an enzyme-responsive drug delivery system for the efficient therapy of breast and pancreatic cancers
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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)
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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.
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- 2017
7. Ultrafast click chemistry with fluorosydnones
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Hui Liu, Davide Audisio, Sarita Forsback, Alain Wagner, Lucie Plougastel, Mourad Elhabiri, Anna Krzyczmonik, David-Alexandre Buisson, Véronique Gouverneur, Frédéric Taran, Oleksandr Koniev, Olof Solin, Sergii Kolodych, and Elodie Decuypere
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010405 organic chemistry ,Electrophilic fluorination ,Kinetics ,Mesoionic ,General Medicine ,General Chemistry ,010402 general chemistry ,Photochemistry ,01 natural sciences ,Combinatorial chemistry ,Catalysis ,Cycloaddition ,0104 chemical sciences ,chemistry.chemical_compound ,Reaction rate constant ,chemistry ,Click chemistry ,Reactivity (chemistry) ,Selectfluor ,ta116 - Abstract
We report the synthesis and reactivity of 4-fluorosydnones, a unique class of mesoionic dipoles displaying exquisite reactivity towards both copper-catalyzed and strain-promoted cycloaddition reactions with alkynes. Synthetic access to these new mesoionic compounds was granted by electrophilic fluorination of σ-sydnone Pd(II) precursors in the presence of Selectfluor. Their reactions with terminal and cyclic alkynes were found to proceed very rapidly and selectively, affording 5-fluoro-1,4-pyrazoles with bimolecular rate constants up to 10(4) m(-1) s(-1) , surpassing those documented in the literature with cycloalkynes. Kinetic studies were carried out to unravel the mechanism of the reaction, and the value of 4-fluorosydnones was further highlighted by successful radiolabeling with [(18) F]Selectfluor.
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- 2016
8. MAPN: First-in-Class Reagent for Kinetically ResolvedThiol-to-Thiol Conjugation.
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Oleksandr Koniev, Sergii Kolodych, Zoljargal Baatarkhuu, Johann Stojko, Jitka Eberova, Jean-Yves Bonnefoy, Sarah Cianférani, Alain Van Dorsselaer, and Alain Wagner
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- 2015
- Full Text
- View/download PDF
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