Search: onr:"swepub:oai:gup.ub.gu.se/337303" > Targeting the Main ...
Fältnamn | Indikatorer | Metadata |
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000 | 09248naa a2200721 4500 | |
001 | oai:gup.ub.gu.se/337303 | |
003 | SwePub | |
008 | 240910s2024 | |||||||||||000 ||eng| | |
009 | oai:DiVA.org:umu-220471 | |
024 | 7 | a https://gup.ub.gu.se/publication/3373032 URI |
024 | 7 | a https://doi.org/10.1021/acschembio.3c007202 DOI |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-2204712 URI |
040 | a (SwePub)gud (SwePub)umu | |
041 | a eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Altincekic, Nadideu Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt am Main, Frankfurt, Germany; Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt am Main, Frankfurt, Germany4 aut |
245 | 1 0 | a Targeting the Main Protease (Mpro, nsp5) by Growth of Fragment Scaffolds Exploiting Structure-Based Methodologies |
264 | 1 | b American Chemical Society (ACS),c 2024 |
520 | a The main protease Mpro, nsp5, of SARS-CoV-2 (SCoV2) is one of its most attractive drug targets. Here, we report primary screening data using nuclear magnetic resonance spectroscopy (NMR) of four different libraries and detailed follow-up synthesis on the promising uracil-containing fragment Z604 derived from these libraries. Z604 shows time-dependent binding. Its inhibitory effect is sensitive to reducing conditions. Starting with Z604, we synthesized and characterized 13 compounds designed by fragment growth strategies. Each compound was characterized by NMR and/or activity assays to investigate their interaction with Mpro. These investigations resulted in the four-armed compound 35b that binds directly to Mpro. 35b could be cocrystallized with Mpro revealing its noncovalent binding mode, which fills all four active site subpockets. Herein, we describe the NMR-derived fragment-to-hit pipeline and its application for the development of promising starting points for inhibitors of the main protease of SCoV2. | |
650 | 7 | a NATURVETENSKAPx Kemix Organisk kemi0 (SwePub)104052 hsv//swe |
650 | 7 | a NATURAL SCIENCESx Chemical Sciencesx Organic Chemistry0 (SwePub)104052 hsv//eng |
650 | 7 | a NATURVETENSKAPx Biologix Biokemi och molekylärbiologi0 (SwePub)106022 hsv//swe |
650 | 7 | a NATURAL SCIENCESx Biological Sciencesx Biochemistry and Molecular Biology0 (SwePub)106022 hsv//eng |
700 | 1 | a Jores, Nathalieu Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt am Main, Frankfurt, Germany; Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt am Main, Frankfurt, Germany4 aut |
700 | 1 | a Löhr, Franku Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt am Main, Frankfurt, Germany; Institute of Biophysical Chemistry, Goethe University Frankfurt am Main, Frankfurt, Germany4 aut |
700 | 1 | a Richter, Christianu Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt am Main, Frankfurt, Germany; Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt am Main, Frankfurt, Germany4 aut |
700 | 1 | a Ehrhardt, Clausu Department of Biochemistry, University of Zurich, Zurich, Switzerland4 aut |
700 | 1 | a Blommers, Marcel J.J.u SavernaTherapeutics, Biel-Benken, Switzerland4 aut |
700 | 1 | a Berg, Hannesu Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt am Main, Frankfurt, Germany; Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt am Main, Frankfurt, Germany4 aut |
700 | 1 | a Öztürk, Sareu Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt am Main, Frankfurt, Germany4 aut |
700 | 1 | a Gande, Santosh L.u Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt am Main, Frankfurt, Germany; Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt am Main, Frankfurt, Germany4 aut |
700 | 1 | a Linhard, Verenau Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt am Main, Frankfurt, Germany; Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt am Main, Frankfurt, Germany4 aut |
700 | 1 | a Orts, Julienu Department of Pharmaceutical Sciences, University of Vienna, Josef-Holaubek-Platz 2, Vienna, Austria4 aut |
700 | 1 | a Abi Saad, Marie Joseu Department of Pharmaceutical Sciences, University of Vienna, Josef-Holaubek-Platz 2, Vienna, Austria4 aut |
700 | 1 | a Bütikofer, Matthiasu Swiss Federal Institute of Technology, Laboratory of Physical Chemistry, ETH Zurich, Zürich, Switzerland4 aut |
700 | 1 | a Kaderli, Janinau Swiss Federal Institute of Technology, Laboratory of Physical Chemistry, ETH Zurich, Zürich, Switzerland4 aut |
700 | 1 | a Karlsson, B Göran,d 1962u Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Svenskt NMR-centrum vid Göteborgs universitet,Department of Chemistry and Molecular Biology,Swedish NMR Centre at Göteborg University,Swedish NMR Centre, Department of Chemistry and Molecular Biology, University of Gothenburg, Göteborg, Sweden; SciLifeLab, University of Gothenburg, Göteborg, Sweden4 aut0 (Swepub:gu)xkargo |
700 | 1 | a Brath, Ulrikau Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Svenskt NMR-centrum vid Göteborgs universitet,Department of Chemistry and Molecular Biology,Swedish NMR Centre at Göteborg University,Swedish NMR Centre, Department of Chemistry and Molecular Biology, University of Gothenburg, Göteborg, Sweden4 aut0 (Swepub:gu)xbraul |
700 | 1 | a Hedenström, Mattias,d 1976-u Umeå universitet,Kemiska institutionen4 aut0 (Swepub:umu)mashem96 |
700 | 1 | a Gröbner, Gerhardu Umeå universitet,Kemiska institutionen4 aut0 (Swepub:umu)gegr0001 |
700 | 1 | a Sauer, Uwe H.u Umeå universitet,Kemiska institutionen4 aut0 (Swepub:umu)uwsa0001 |
700 | 1 | a Perrakis, Anastassisu Oncode Institute and Division of Biochemistry, The Netherlands Cancer Institute, Amsterdam, Netherlands4 aut |
700 | 1 | a Langer, Julianu Max Planck Institute of Biophysics, Frankfurt am Main, Germany4 aut |
700 | 1 | a Banci, Luciau Magnetic Resonance Center and Department of Chemistry, University of Florence, Via L. Sacconi 6, Sesto Fiorentino, Italy; Consorzio Interuniversitario Risonanze Magnetiche Metalloproteine, Via L. Sacconi 6, Sesto Fiorentino, Italy4 aut |
700 | 1 | a Cantini, Francescau Magnetic Resonance Center and Department of Chemistry, University of Florence, Via L. Sacconi 6, Sesto Fiorentino, Italy; Consorzio Interuniversitario Risonanze Magnetiche Metalloproteine, Via L. Sacconi 6, Sesto Fiorentino, Italy4 aut |
700 | 1 | a Fragai, Marcou Magnetic Resonance Center and Department of Chemistry, University of Florence, Via L. Sacconi 6, Sesto Fiorentino, Italy; Consorzio Interuniversitario Risonanze Magnetiche Metalloproteine, Via L. Sacconi 6, Sesto Fiorentino, Italy4 aut |
700 | 1 | a Grifagni, Deborahu Magnetic Resonance Center and Department of Chemistry, University of Florence, Via L. Sacconi 6, Sesto Fiorentino, Italy4 aut |
700 | 1 | a Barthel, Tatjanau Macromolecular Crystallography, Helmholtz-Zentrum Berlin, Albert-Einstein-Str. 15, Berlin, Germany4 aut |
700 | 1 | a Wollenhaupt, Janu Macromolecular Crystallography, Helmholtz-Zentrum Berlin, Albert-Einstein-Str. 15, Berlin, Germany4 aut |
700 | 1 | a Weiss, Manfred S.u Macromolecular Crystallography, Helmholtz-Zentrum Berlin, Albert-Einstein-Str. 15, Berlin, Germany,Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt am Main, Frankfurt, Germany; Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt am Main, Frankfurt, Germany4 aut |
700 | 1 | a Robertson, Angusu NIH, LCP NIDDK, MD, Bethesda, United States4 aut |
700 | 1 | a Bax, Adriaanu NIH, LCP NIDDK, MD, Bethesda, United States4 aut |
700 | 1 | a Sreeramulu, Sridhar4 aut |
700 | 1 | a Schwalbe, Haraldu Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt am Main, Frankfurt, Germany; Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt am Main, Frankfurt, Germany4 aut |
710 | 2 | a Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt am Main, Frankfurt, Germany; Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt am Main, Frankfurt, Germanyb Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt am Main, Frankfurt, Germany; Institute of Biophysical Chemistry, Goethe University Frankfurt am Main, Frankfurt, Germany4 org |
773 | 0 | t ACS Chemical Biologyd : American Chemical Society (ACS)g 19:2, s. 563-574q 19:2<563-574x 1554-8929x 1554-8937 |
856 | 4 | u https://doi.org/10.1021/acschembio.3c00720y Fulltext |
856 | 4 | u https://umu.diva-portal.org/smash/get/diva2:1838232/FULLTEXT02.pdfx primaryx Raw objecty fulltext:print |
856 | 4 8 | u https://gup.ub.gu.se/publication/337303 |
856 | 4 8 | u https://doi.org/10.1021/acschembio.3c00720 |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-220471 |
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