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结构变化对抗菌活性和细胞毒性的影响,原因是仿真HnMc中的替代物

Seong-Cheol Park¹, Jong-Kook Lee¹, Young-Min Kim¹

¹Department of Chemical Engineering, Sunchon National University, Suncheon, 57922, Republic of Korea.

Biochemical and biophysical research communications

|September 11, 2023

概括

抗微生物 (AMP) 是有希望的下一代抗生素. 像HnMc-WP2这样的AMP的修改增强了抗菌活性,降低了毒性,并且在体内显示出对耐药细菌的有效性.

科学领域:

生物化学生物化学
分子生物学分子生物学
药物发现药物发现药物发现

背景情况:

多抗药性病原体需要新的抗生素策略.
自然存在的抗微生物 (AMP) 往往具有高毒性和有限的疗效.
氨基酸替代可以改善AMP的抗菌活性和选择性.

研究的目的:

研究特定氨基酸替代物对仿制抗微生物的结构活性关系的影响.
开发具有增强抗菌功效,盐耐受性和降低细胞毒性的新型AMP.
评估修改后的AMP对抗耐药细菌的体外和体内疗效.

主要方法:

用向氨基酸替代物设计和合成修改后的化学 (HnMc-W,HnMc-WP1,HnMc-WP2).
在体外对抗微生物活性,盐耐受性和细胞毒性的评估.
基修饰的结构分析,包括螺旋结构和灵活性.
在体内有效性测试使用感染耐药Pseudomonas aeruginosa的小鼠模型.

主要成果:

HnMc-W证明了膜解作用和改善了盐分耐受性.
HnMc-WP1表现出增强的耐盐抗菌作用和减少细胞毒性,这是由于proline-kink螺旋结构.
具有PXXP动机的HnMc-WP2在体外表现出卓越的抗菌活性,没有细胞毒性.
在 Pseudomonas aeruginosa 小鼠感染模型中,HnMc-WP2 显示出强大的抗菌作用.

结论:

特定的氨基酸替代物显著调节AMP的特性,包括活性,选择性和稳定性.
HnMc-WP2是下一代抗生素的有希望的候选者,因为它具有强大和选择性的抗菌作用.
这些发现为设计优化抗微生物来对抗耐药性感染提供了宝贵的见解.

关键词:

抗微生物是一种抗微生物.化学化学的酸.螺旋螺旋结构结构基克结构结构的基克结构.在PXXP图案中,PXXP是PXXP图案.

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