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To tackle these, we develop targeted delivery of antimicrobial compounds. The drug of choice is mitomycin C, which has documented activity against persister cells. For targeting, we use vancomycin, a compound that binds the bacterial cell wall. The linker between the two contains a scissile disulfide bond for drug release. The conjugate is optimized as regards the site of drug attachment to vancomycin. The lead conjugate is shown to be a broad\u2010spectrum antibacterial agent with activity against Gram\u2010positive strains, including vancomycin intermediate and resistant ones, as well as Gram\u2010negative strains and the bacterial biofilm. In vitro, antimicrobial effects of the targeted mitomycin treatment are shown to be significantly more potent compared to the free drug; at the same time, the non\u2010specific cytotoxicity to mammalian cells is significantly decreased. In vivo evaluation in the implant\u2010associated osteomyelitis model in mice reveals robust targeting and good tolerance to the treatment with no signs of toxicity. However, the limited therapeutic efficacy indicates that more work is needed to match the developed treatment to an appropriate disease model.<\/jats:p>","DOI":"10.1002\/adhm.202503932","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T07:31:26Z","timestamp":1765265486000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Broad\u2010Spectrum Antimicrobial Treatment Targeted Through Drug Conjugation to Vancomycin"],"prefix":"10.1002","volume":"15","author":[{"given":"Magnus Schou","family":"Dybtved","sequence":"first","affiliation":[{"name":"Department of Chemistry Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maiken E.","family":"Petersen","sequence":"additional","affiliation":[{"name":"Interdisciplinary Nanoscience Centre (iNANO) Aarhus University  Aarhus 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