125300 20241125101151.0 doi 10.1038/s41467-023-36598-7 sideral 132938 ART-2023-132938 eng Madriz Sørensen, D. Identification of global inhibitors of cellular glycosylation 2023 Access copy available to the general public Unrestricted Small molecule inhibitors of glycosylation enzymes are valuable tools for dissecting glycan functions and potential drug candidates. Screening for inhibitors of glycosyltransferases are mainly performed by in vitro enzyme assays with difficulties moving candidates to cells and animals. Here, we circumvent this by employing a cell-based screening assay using glycoengineered cells expressing tailored reporter glycoproteins. We focused on GalNAc-type O-glycosylation and selected the GalNAc-T11 isoenzyme that selectively glycosylates endocytic low-density lipoprotein receptor (LDLR)-related proteins as targets. Our screen of a limited small molecule compound library did not identify selective inhibitors of GalNAc-T11, however, we identify two compounds that broadly inhibited Golgi-localized glycosylation processes. These compounds mediate the reversible fragmentation of the Golgi system without affecting secretion. We demonstrate how these inhibitors can be used to manipulate glycosylation in cells to induce expression of truncated O-glycans and augment binding of cancer-specific Tn-glycoprotein antibodies and to inhibit expression of heparan sulfate and binding and infection of SARS-CoV-2. info:eu-repo/grantAgreement/ES/DGA-FEDER/E34-R17 info:eu-repo/grantAgreement/ES/DGA/LMP58-18 info:eu-repo/grantAgreement/EC/FP7/609409/EU/Supporting transnational mobility within the European life sciences by cofunding of the EMBO Fellowship Programme/LTFCOFUND2013 info:eu-repo/grantAgreement/EC/H2020/787684/EU/Generation of a Cell-Based Sialoglycan Array to Decipher Biological Interactions and Functions of the Human Sialome/Sialoglycan Array This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 787684-Sialoglycan Array info:eu-repo/grantAgreement/ES/MICINN/BFU2016-75633-P info:eu-repo/grantAgreement/ES/MICINN/PID2019-105451GB-I00 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 14.7 2023 MULTIDISCIPLINARY SCIENCES 8 / 134 = 0.06 2023 Q1 T1 4.887 2023 Biochemistry, Genetics and Molecular Biology (miscellaneous) 2023 Q1 Physics and Astronomy (miscellaneous) 2023 Q1 Chemistry (miscellaneous) 2023 Q1 24.9 2023 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Büll, C. Madsen, T. D. Lira-Navarrete, E. Clausen, T. M. Clark, A. E. Garretson, A. F. Karlsson, R. Pijnenborg, J. F. A. Yin, X. Miller, R. L. Chanda, S. K. Boltje, T. J. Schjoldager, K. T. Vakhrushev, S. Y. Halim, A. Esko, J. D. Carlin, A. F. Hurtado-Guerrero, R. (orcid)0000-0002-3122-9401 Weigert, R. Clausen, H. Narimatsu, Y. 14 (2023), 948 [19 pp.] Nature communications 2041-1723 3856781 http://zaguan.unizar.es/record/125300/files/texto_completo.pdf Versión publicada 2519072 http://zaguan.unizar.es/record/125300/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:125300 articulos driver 2024-11-22-12:06:55 ARTICLE