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However, available drugs specifically developed for the effective inhibition or degradation of ZBP1 is still lacking so far. In this study, we developed a potent covalent recognition\u2010based PROTAC (C\u2010PROTAC) molecule for the degradation of ZBP1. It consists of a DNA aptamer as the recognition moiety and an E3 enzyme\u2010recruiting unit, connected by a linker containing\n                    <jats:italic>N<\/jats:italic>\n                    \u2010acyl\u2010\n                    <jats:italic>N<\/jats:italic>\n                    \u2010alkyl sulfonamides (NASA) groups. The DNA aptamer specifically binds to ZBP1, while the NASA\u2010containing linker facilitates the formation of a covalent bond between the PROTAC and the target protein. The E3 ligase\u2010recruiting unit then directs the ubiquitin\u2010proteasome system to degrade the ZBP1\u2010PROTAC complex. This approach combines the high specificity of DNA aptamers with the efficiency of covalent binding and the degradation\u2010inducing capabilities of PROTACs, providing a powerful tool for targeted protein degradation. The successful application of this technology to ZBP1 highlights its potential for the selective elimination of disease\u2010associated proteins and the development of novel therapeutic strategies.\n                  <\/jats:p>","DOI":"10.1002\/anie.202423524","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T03:21:42Z","timestamp":1741749702000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Targeted Degradation of ZBP1 with Covalent PROTACs for Anti\u2010Inflammatory Treatment of Infections"],"prefix":"10.1002","volume":"64","author":[{"given":"Rentang","family":"Huang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology Frontiers Science Centre for New Organic Matter Tianjin Key Laboratory of Biosensing and Molecular Recognition Research Centre for Analytical Sciences College of Chemistry School of Medicine and Frontiers Science Centre for Cell Responses Nankai University  Tianjin 300071 P.R. 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