S-Nitrosothiol-modified nitric oxide-releasing chitosan oligosaccharides as antibacterial agents.
S-Nitrosothiol-modified nitric oxide-releasing chitosan oligosaccharides as antibacterial agents.
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DOI：
10.1016/j.actbio.2014.10.028
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发表时间：
2015-01
影响因子：
9.7
通讯作者：
Schoenfisch MH
中科院分区：
文献类型：
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作者：
Lu Y;Shah A;Hunter RA;Soto RJ;Schoenfisch MH
通过与2 - 亚氨基硫杂环戊烷盐酸盐和3 - 乙酰氨基 - 4,4 - 二甲基硫杂环丁烷 - 2 - 酮反应，随后进行巯基亚硝化，合成了S - 亚硝基硫醇修饰的壳寡糖。所得的释放一氧化氮（NO）的壳寡糖储存约0.3 μmol NO/mg壳寡糖。利用亚硝基硫醇的化学结构（即伯和叔结构）以及使用抗坏血酸作为NO供体分解的触发剂来控制NO释放动力学。在有抗坏血酸的情况下，S - 亚硝基硫醇修饰的壳寡糖使铜绿假单胞菌（P. aeruginosa）的活力降低4个对数级。共聚焦显微镜显示，与叔S - 亚硝基硫醇体系相比，伯S - 亚硝基硫醇修饰的壳寡糖与细菌的结合更多。在使细菌活力降低4个对数级所需的浓度下，伯S - 亚硝基硫醇修饰的壳寡糖对L929小鼠成纤维细胞的毒性极小，进一步证明了S - 亚硝基硫醇修饰的壳寡糖作为NO释放治疗剂的潜力。
S-nitrosothiol-modified chitosan oligosaccharides were synthesized by reaction with 2-iminothiolane hydrochloride and 3-acetamido-4,4-dimethylthietan-2-one, followed by the thiol nitrosation. The resulting nitric oxide (NO)-releasing chitosan oligosaccharides stored ~0.3 μmol NO/mg chitosan. Both the chemical structure of the nitrosothiol (i.e., primary and tertiary) and the use of ascorbic acid as a trigger for NO donor decomposition were used to control the NO-release kinetics. With ascorbic acid, the S-nitrosothiol-modified chitosan oligosaccharides elicited a 4-log reduction in Pseudomonas aeruginosa (P. aeruginosa) viability. Confocal microscopy indicated that the primary S-nitrosothiol-modified chitosan oligosaccharides associated more with the bacteria relative to the tertiary S-nitrosothiol system. The primary S-nitrosothiol-modified chitosan oligosaccharides elicited minimal toxicity towards L929 mouse fibroblast cells at the concentration necessary for a 4-log reduction in bacterial viability, further demonstrating the potential of S-nitrosothiol-modified chitosan oligosaccharides as NO-release therapeutics.