聚合物的二次结构对抗菌疗效和抗生素强化作用的作用
Swagatam Barman1,2, Alimi Abiodun1, Md Waliullah Hossain1
1Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina 29208, United States.
bioRxiv : the preprint server for biology
|November 28, 2024
概括
状螺旋聚合物对抗药物耐药细菌具有增强的抗菌活性. 这一发现为打击抗生素耐药性和生物膜形成提供了新的策略.
科学领域:
- 生物化学 生物化学
- 聚合物化学 聚合物化学
- 微生物学 微生物学
背景情况:
- 抗生素耐药性,生物膜形成和休眠的细菌种群是全球健康的关键问题.
- 合成抗微生物 (AMP) 模仿物是潜在的替代品,但二次结构在它们的有效性中的作用尚不清楚.
研究的目的:
- 调查α-聚合物中性控制的二次结构对它们的抗菌疗效的影响.
- 探索这些聚合物的潜力,作为传统抗生素的替代品.
主要方法:
- 通过环开聚合和乙烯点击化学合成性控制的α-聚合物 (D-PP和DL-PP).
- 在仿生条件下评估聚合物结构 (螺旋式与随机).
- 评估抗菌活性,抗生素强化,溶血活性,蛋白酶稳定性,膜相互作用以及对休眠细菌和生物膜的疗效.
主要成果:
- D-PP采用了稳定的螺旋结构,而DL-PP仍然是随机的.
- 螺旋式D-PP表现出增强的抗菌和抗生素强化活性 (增加2至256倍) 对抗多药耐药的格拉姆阴性病原体.
- D-PP表现出更大的膜相互作用,低血解活性和高蛋白酶稳定性.
- D-PP和抗生素的组合消除了休眠的细菌,破坏了生物膜,并最大限度地减少了抗菌素耐药性的发展.
结论:
- 在α-聚合物中,以性驱动的螺旋结构显著增强了抗微生物药物的有效性.
- 这些基于多的药物为打击抗生素耐药性和生物膜相关感染提供了有希望的策略.
- 这些发现支持通过利用二次结构特征,合理设计新型抗菌剂.
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