000125300 001__ 125300 000125300 005__ 20240705134213.0 000125300 0247_ $$2doi$$a10.1038/s41467-023-36598-7 000125300 0248_ $$2sideral$$a132938 000125300 037__ $$aART-2023-132938 000125300 041__ $$aeng 000125300 100__ $$aMadriz Sørensen, D. 000125300 245__ $$aIdentification of global inhibitors of cellular glycosylation 000125300 260__ $$c2023 000125300 5060_ $$aAccess copy available to the general public$$fUnrestricted 000125300 5203_ $$aSmall 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. 000125300 536__ $$9info:eu-repo/grantAgreement/ES/MICINN/PID2019-105451GB-I00$$9info:eu-repo/grantAgreement/ES/MICINN/BFU2016-75633-P$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 787684-Sialoglycan Array$$9info: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$$9info:eu-repo/grantAgreement/EC/FP7/609409/EU/Supporting transnational mobility within the European life sciences by cofunding of the EMBO Fellowship Programme/LTFCOFUND2013$$9info:eu-repo/grantAgreement/ES/DGA/LMP58-18$$9info:eu-repo/grantAgreement/ES/DGA-FEDER/E34-R17 000125300 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/ 000125300 592__ $$a4.887$$b2023 000125300 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2023$$dQ1 000125300 593__ $$aPhysics and Astronomy (miscellaneous)$$c2023$$dQ1 000125300 593__ $$aChemistry (miscellaneous)$$c2023$$dQ1 000125300 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000125300 700__ $$aBüll, C. 000125300 700__ $$aMadsen, T. D. 000125300 700__ $$aLira-Navarrete, E. 000125300 700__ $$aClausen, T. M. 000125300 700__ $$aClark, A. E. 000125300 700__ $$aGarretson, A. F. 000125300 700__ $$aKarlsson, R. 000125300 700__ $$aPijnenborg, J. F. A. 000125300 700__ $$aYin, X. 000125300 700__ $$aMiller, R. L. 000125300 700__ $$aChanda, S. K. 000125300 700__ $$aBoltje, T. J. 000125300 700__ $$aSchjoldager, K. T. 000125300 700__ $$aVakhrushev, S. Y. 000125300 700__ $$aHalim, A. 000125300 700__ $$aEsko, J. D. 000125300 700__ $$aCarlin, A. F. 000125300 700__ $$0(orcid)0000-0002-3122-9401$$aHurtado-Guerrero, R. 000125300 700__ $$aWeigert, R. 000125300 700__ $$aClausen, H. 000125300 700__ $$aNarimatsu, Y. 000125300 773__ $$g14 (2023), 948 [19 pp.]$$tNature communications$$x2041-1723 000125300 8564_ $$s3856781$$uhttps://zaguan.unizar.es/record/125300/files/texto_completo.pdf$$yVersión publicada 000125300 8564_ $$s2519072$$uhttps://zaguan.unizar.es/record/125300/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000125300 909CO $$ooai:zaguan.unizar.es:125300$$particulos$$pdriver 000125300 951__ $$a2024-07-05-12:52:12 000125300 980__ $$aARTICLE