细菌转糖酶抑制剂的亲和性选
Wei-Shen Wu1,2, Wei-Chieh Cheng2, Ting-Jen R Cheng2
1Graduate Institute of Life Sciences, National Defense Medical Center , 161 Minquan E. Road, Section 6, Neihu, Taipei 114, Taiwan.
Journal of the American Chemical Society
|February 8, 2018
概括
研究人员开发了一种新方法来发现针对细菌转糖酶的新型抗生素. 这种查发现了强效的抗菌化合物,包括对抗性细菌有效的贝纳斯衍生物和阿尔博金.
科学领域:
- 医学化学
- 微生物学
- 药物发现
背景情况:
- 抗生素耐药性是一个全球危机,需要开发新的抗菌剂.
- 需要新抗生素来对抗耐药细菌感染.
研究的目的:
- 开发一种基于亲缘关系的配体选方法来识别新的抗生素.
- 针对之前未知的细菌表面转糖酶酶.
- 从复杂的天然产品库中分离出强大的抗菌化合物.
主要方法:
- 使用在珠子上固定的青素结合蛋白进行基于亲和性的选.
- 使用质谱测量用于化合物识别和表征.
- 使用moenomycin A和salicylanilide类似物作为参考抑制剂进行比较测试.
主要成果:
- 成功分离了四种强效的抗菌化合物:贝纳斯衍生物 (11-13) 和阿尔博丁 (14).
- 化合物11和14对格兰正和格兰阴性细菌具有广泛的疗效.
- 这些化合物对具有挑战性的病原体有效,包括Acinetobacter baumannii,Clostridium difficile和Staphylococcus aureus,包括耐药菌株,具有微小到纳米最小的抑制度.
结论:
- 开发的基于亲和力的选方法对发现新型抗生素有效.
- 贝纳沙丁衍生物和阿尔博金是新抗生素开发的有希望的候选药物.
- 这些化合物显示出治疗多药耐药细菌引起的感染的巨大潜力.
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