{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T01:52:23Z","timestamp":1760233943031,"version":"build-2065373602"},"reference-count":36,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T00:00:00Z","timestamp":1615420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Osteomyelitis and orthopedic infections are major clinical problems, limited by a lack of antibiotics specialized for such applications. In this paper, we describe the design and synthesis of a novel bone-binding antibiotic (BBA-1) and its subsequent structural and functional characterization. The synthesis of BBA-1 was the result of a two-step chemical conjugation of cationic selective antimicrobial-90 (CSA-90) and the bisphosphonate alendronate (ALN) via a heterobifunctional linker. This was analytically confirmed by HPLC, FT-IR, MS and NMR spectroscopy. BBA-1 showed rapid binding and high affinity to bone mineral in an in vitro hydroxyapatite binding assay. Kirby\u2014Baur assays confirmed that BBA-1 shows a potent antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus comparable to CSA-90. Differentiation of cultured osteoblasts in media supplemented with BBA-1 led to increased alkaline phosphatase expression, which is consistent with the pro-osteogenic activity of CSA-90. Bisphosphonates, such as ALN, are inhibitors of protein prenylation, however, the amine conjugation of ALN to CSA-90 disrupted this activity in an in vitro protein prenylation assay. Overall, these findings support the antimicrobial, bone-binding, and pro-osteogenic activities of BBA-1. The compound and related agents have the potential to ensure lasting activity against osteomyelitis after systemic delivery.<\/jats:p>","DOI":"10.3390\/molecules26061541","type":"journal-article","created":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T20:17:40Z","timestamp":1615493860000},"page":"1541","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Synthesis and Characterization of Bone Binding Antibiotic-1 (BBA-1), a Novel Antimicrobial for Orthopedic Applications"],"prefix":"10.3390","volume":"26","author":[{"given":"Sumedh","family":"Kamble","sequence":"first","affiliation":[{"name":"Bioengineering and Molecular Medicine Laboratory, Kids Research at The Children\u2019s Hospital at Westmead, Westmead, NSW 2145, Australia"},{"name":"Discipline of Child and Adolescent Medicine, Sydney Medical School, University of Sydney, Sydney, NSW 2050, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2622-5721","authenticated-orcid":false,"given":"Peter","family":"Valtchev","sequence":"additional","affiliation":[{"name":"School of Chemical and Biomolecular Engineering, University of Sydney, Camperdown, NSW 2008, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0631-2975","authenticated-orcid":false,"given":"Aiken","family":"Dao","sequence":"additional","affiliation":[{"name":"Bioengineering and Molecular Medicine Laboratory, Kids Research at The Children\u2019s Hospital at Westmead, Westmead, NSW 2145, Australia"},{"name":"Discipline of Child and Adolescent Medicine, Sydney Medical School, University of Sydney, Sydney, NSW 2050, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2426-5009","authenticated-orcid":false,"given":"Th\u00e9ophile","family":"Pelras","sequence":"additional","affiliation":[{"name":"Key Centre for Polymers and Colloids, School of Chemistry and Sydney Nano, University of Sydney, Camperdown, NSW 2006, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J","family":"Rogers","sequence":"additional","affiliation":[{"name":"Garvan Institute of Medical Research, St. Vincent\u2019s Clinical School, Faculty of Medicine, University of New South Wales, Darlinghurst, NSW 2010, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul B.","family":"Savage","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84601, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fariba","family":"Dehghani","sequence":"additional","affiliation":[{"name":"School of Chemical and Biomolecular Engineering, University of Sydney, Camperdown, NSW 2008, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aaron","family":"Schindeler","sequence":"additional","affiliation":[{"name":"Bioengineering and Molecular Medicine Laboratory, Kids Research at The Children\u2019s Hospital at Westmead, Westmead, NSW 2145, Australia"},{"name":"Discipline of Child and Adolescent Medicine, Sydney Medical School, University of Sydney, Sydney, NSW 2050, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1302\/0301-620X.89B5.19170","article-title":"A history of osteomyelitis from the Journal of Bone and Joint Surgery","volume":"89-B","author":"Klenerman","year":"2007","journal-title":"J. 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