Publications
Synthesis and Characterization of Bone Binding Antibiotic-1 (BBA-1), a Novel Antimicrobial for Orthopedic Applications
Abstract
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-Baur 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.
Type | Journal |
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ISBN | 1420-3049 (Electronic) 1420-3049 (Linking) |
Authors | Kamble, S.; Valtchev, P.; Dao, A.; Pelras, T.; Rogers, M. J.; Savage, P. B.; Dehghani, F.; Schindeler, A. |
Responsible Garvan Author | Professor Mike Rogers |
Publisher Name | MOLECULES |
Published Date | 2021-03-31 |
Published Volume | 26 |
Published Issue | 6 |
Status | Published in-print |
DOI | 10.3390/molecules26061541 |
URL link to publisher's version | https://www.ncbi.nlm.nih.gov/pubmed/33799713 |