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Design, solid-phase synthesis and evaluation of enterobactin analogs for iron delivery into the human pathogen Campylobacter jejuni
Bioorganic & Medicinal Chemistry ( IF 3.3 ) Pub Date : 2018-04-16 , DOI: 10.1016/j.bmc.2018.04.030
Cristina Y Zamora 1 , Amaël G E Madec 1 , Wilma Neumann 2 , Elizabeth M Nolan 2 , Barbara Imperiali 1
Affiliation  

The human enteropathogen Campylobacter jejuni, like many bacteria, employs siderophores such as enterobactin for cellular uptake of ferric iron. This transport process has been shown to be essential for virulence and presents an attractive opportunity for further study of the permissiveness of this pathway to small-molecule intervention and as inspiration for the development of synthetic carriers that may effectively transport cargo into Gram-negative bacteria. In this work, we have developed a facile and robust microscale assay to measure growth recovery of C. jejuni NCTC 11168 in liquid culture as a result of ferric iron uptake. In parallel, we have established the solid-phase synthesis of catecholamide compounds modeled on enterobactin fragments. Applying these methodological developments, we show that small synthetic iron chelators of minimal dimensions provide ferric iron to C. jejuni with equal or greater efficiency than enterobactin.



中文翻译:


用于将铁输送到人类病原体空肠弯曲菌中的肠杆菌素类似物的设计、固相合成和评估



人类肠道病原体空肠弯曲菌与许多细菌一样,利用铁载体(例如肠杆菌素)来细胞摄取三价铁。这种运输过程已被证明对于毒力至关重要,并为进一步研究这种小分子干预途径的允许性提供了一个有吸引力的机会,并为开发可有效地将货物运输到革兰氏阴性细菌中的合成载体提供了灵感。在这项工作中,我们开发了一种简便而强大的微量测定法,用于测量液体培养物中空肠弯曲菌NCTC 11168 由于三价铁吸收而导致的生长恢复。与此同时,我们建立了以肠杆菌素片段为模型的儿茶酚酰胺化合物的固相合成方法。应用这些方法学进展,我们表明,最小尺寸的小型合成铁螯合剂以与肠杆菌素相同或更高的效率向空肠弯曲菌提供三价铁。

更新日期:2018-04-16
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