New selective inhibitors of cap dependent proteins: Synthesis, delivery and characterisation (Q84205)
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Project Q84205 in Poland
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | New selective inhibitors of cap dependent proteins: Synthesis, delivery and characterisation |
Project Q84205 in Poland |
Statements
4,500,000.0 zloty
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4,500,000.0 zloty
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100.0 percent
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1 June 2017
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30 November 2021
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UNIWERSYTET WARSZAWSKI
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The project aims at the design, synthesis, and evaluation of novel mRNA 5’ cap analogs as selective inhibitors of three major cap-related proteins: the eukaryotic translation initiation factor 4E (eIF4E) and the two decapping enzymes (DcpS and Dcp2). The proteins were selected due to their key roles in mRNA function and an already-confirmed status as molecular targets for cancer and neuromuscular diseases. To achieve the goal, we propose a comprehensive approach encompassing 1) generation of novel cap derivatives, either by traditional chemical synthesis or by combinatorial approach based on in situ click chemistry, 2) ideas for novel molecular probes and screening approaches specifically tailored for each of the proteins, 3) in-depth evaluation of the found inhibitors using biophysical, biochemical, and structural methods to understand their mechanism of action at the molecular level, 4) application of several cell-delivery strategies to demonstrate the biological potential in vivo. (Polish)
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The project aims at the design, synthesis, and evaluation of novel mRNA 5' cap analogs as selective inhibitors of three major cap-related proteins: the eukaryotic translation initiation factor 4E (eIF4E) and the two decapping enzymes (DCPS and Dcp2). The proteins were selected due to their key roles in mRNA function and an already-confirmed status as molecular targets for cancer and neuromuscular diseases. To achieve the goal, we propose a comprehensive approach encompassing 1) generation of novel cap derivatives, either by traditional chemical synthesis or by combinatorial approach based on in situ click chemistry, 2) ideas for novel molecular probes and screening approaches specifically tailored for each of the proteins, 3) in-depth evaluation of the found inhibitors using biophysical, biochemical, and structural methods to understand their mechanism of action at the molecular level, 4) application of several cell-delivery strategies in the demonstrate. (English)
14 October 2020
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Le projet vise à concevoir, à synthétiser et à évaluer de nouveaux analogues de capuchon d’ARNm 5’en tant qu’inhibiteurs sélectifs de trois principales protéines liées au cap: le facteur d’initiation de la traduction eucararyotique 4E (eIF4E) et les deux enzymes de décachage (DCPS et Dcp2). Les protéines ont été sélectionnées en raison de leur rôle clé dans la fonction de l’ARNm et d’un statut déjà confirmé en tant que cibles moléculaires pour le cancer et les maladies neuromusculaires. Pour atteindre cet objectif, nous proposons une approche globale comprenant 1) la génération de nouveaux dérivés de capuchon, soit par synthèse chimique traditionnelle, soit par une approche combinée basée sur la chimie par clic in situ, 2) des idées de nouvelles sondes moléculaires et des approches de dépistage spécifiquement adaptées à chacune des protéines, 3) une évaluation approfondie des inhibiteurs trouvés à l’aide de méthodes biophysiques, biochimiques et structurelles pour comprendre leur mécanisme d’action au niveau moléculaire, 4) de l’application de plusieurs stratégies de délivrance de cellules pour démontrer le potentiel biologique in vivo. (French)
30 November 2021
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Identifiers
POIR.04.04.00-00-20A2/16
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