设计、固相合成及评估用于将铁递送入人类病原体空肠弯曲菌的依沙菌素类似物。
Design, solid-phase synthesis and evaluation of enterobactin analogs for iron delivery into the human pathogen Campylobacter jejuni.
机构信息
Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
出版信息
Bioorg Med Chem. 2018 Oct 15;26(19):5314-5321. doi: 10.1016/j.bmc.2018.04.030. Epub 2018 Apr 16.
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.
人类病原体空肠弯曲菌像许多细菌一样，利用肠菌素等铁载体来摄取细胞内的三价铁。这一运输过程对毒力至关重要，为进一步研究该途径对小分子干预的允许性以及为开发可能有效将货物输送到革兰氏阴性菌的合成载体提供了机会。在这项工作中，我们开发了一种简单而强大的微量测定法，以测量液体培养中由于三价铁摄取而导致的空肠弯曲菌 NCTC 11168 的生长恢复。同时，我们建立了基于肠菌素片段的儿茶酚酰胺化合物的固相合成。应用这些方法学的发展，我们表明，最小尺寸的小型合成铁螯合剂与肠菌素一样，甚至更有效地为空肠弯曲菌提供三价铁。
Zotero 插件