{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:52:25Z","timestamp":1792072345473,"version":"4.4.0"},"reference-count":40,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22407140"],"award-info":[{"award-number":["22407140"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    O\u2010GlcNAcylation is an important post\u2010translational modification that regulates numerous cellular processes, yet tools enabling selective removal of O\u2010GlcNAc from individual proteins via endogenous O\u2010GlcNAcase (OGA) in living cells remain limited. Here, we report De\u2010O\u2010GlcNAcylation\u2010targeting chimeras (DOGTACs), a chemically induced proximity strategy that selectively reduces O\u2010GlcNAc from target proteins by recruiting endogenous OGA. Initial designs incorporating potent competitive OGA inhibitors efficiently engaged OGA but failed to induce de\u2010O\u2010GlcNAcylation, revealing that catalytic competence is essential for productive proximity\u2010driven editing. By attenuating inhibitor potency while retaining OGA engagement, we developed optimized DOGTACs that promote concentration\u2010 and time\u2010dependent, target\u2010specific de\u2010O\u2010GlcNAcylation in living cells without perturbing global O\u2010GlcNAc levels. Furthermore, we successfully applied DOGTAC to additional target proteins including FKBP12\n                    <jats:sup>F36V<\/jats:sup>\n                    fused proteins and endogenous CK2\u03b1 across different cell lines. Besides, we found DOGTAC (R)\u2010C4 treatment could reduce the stability of FKBP12\n                    <jats:sup>F36V<\/jats:sup>\n                    fused\u2010NUP98\u2010KDM5A in cells. Collectively, this work established attenuated competitive inhibitors as recruitment modules for catalytic enzyme engagement and a novel strategy, DOGTAC, for targeted de\u2010O\u2010GlcNAcylation via endogenous OGA recruitment in living cells.\n                  <\/jats:p>","DOI":"10.1002\/anie.1827729","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:35:38Z","timestamp":1792071338000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Proximity\u2010Induced Protein Deglycosylation by Endogenous O\u2010GlcNAcase"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9239-6281","authenticated-orcid":false,"given":"Haixing","family":"Xu","sequence":"first","affiliation":[{"name":"Guangdong\u2010Hong Kong\u2010Macao Joint Laboratory for New Drug Screening School of Pharmacy The Chinese University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3177-9966","authenticated-orcid":false,"given":"Bowen","family":"Ma","sequence":"additional","affiliation":[{"name":"Guangdong\u2010Hong Kong\u2010Macao Joint Laboratory for New Drug Screening School of Pharmacy The Chinese University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunpeng","family":"Huang","sequence":"additional","affiliation":[{"name":"Guangdong\u2010Hong Kong\u2010Macao Joint Laboratory for New Drug Screening School of Pharmacy The Chinese University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialin","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Proteomics National Center for Protein Sciences (Beijing)  Beijing 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