Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, United States.
Bioconjug Chem. 2010 Nov 17;21(11):1978-86. doi: 10.1021/bc100136e. Epub 2010 Oct 15.
Infections are a devastating complication of titanium alloy orthopedic implants. Current therapy includes antibiotic-impregnated bone cement and antibiotic-containing coatings. We hypothesized that daptomycin, a Gram-positive peptide antibiotic, could prevent bacterial colonization on titanium alloy surfaces if covalently bonded via a flexible, hydrophilic spacer. We designed and synthesized a series of daptomycin conjugates for bonding to the surface of 1.0 cm² Ti6Al4V foils through bisphosphonate groups, reaching a maximum yield of 180 pmol/cm². Daptomycin-bonded foils killed 53 ± 5% of a high challenge dose of 3 × 10⁵ cfu Staphylococcus aureus ATCC 29213.
感染是钛合金骨科植入物的一种破坏性并发症。目前的治疗方法包括抗生素浸渍骨水泥和含抗生素的涂层。我们假设达托霉素，一种革兰氏阳性肽抗生素，如果通过柔性、亲水性间隔物共价结合，可以防止细菌在钛合金表面定植。我们设计并合成了一系列达托霉素缀合物，通过双膦酸盐基团与 1.0 cm² Ti6Al4V 箔表面结合，达到了 180 pmol/cm²的最大产率。结合达托霉素的箔片杀死了 3 × 10⁵ cfu 的金黄色葡萄球菌 ATCC 29213 的高挑战剂量的 53 ± 5%。
