Design, solid-phase synthesis and evaluation of enterobactin analogs for iron delivery into the human pathogen Campylobacter jejuni. Issue 19 (15th October 2018)

• Record Type: Journal Article
• Authors: Zamora, Cristina Y.; Madec, Amaël G.E.; Neumann, Wilma; Nolan, Elizabeth M.; Imperiali, Barbara
• Is Part Of: Bioorganic & medicinal chemistry. Volume 26:Issue 19(2018)
• Page Start: 5314
• Page End: 5321
• Publication Date: 2018-10-15
• Subjects: BP 2, 2′-bipyridine -- CH2Cl2 dichloromethane -- Cipro ciprofloxacin -- DIPEA N, N-diisopropylethylamine -- DMF dimethylformamide -- DMSO dimethylsulfoxide -- ICP-MS inductively coupled plasma mass spectrometry -- MeCN acetonitrile -- MEM-α minimal essential medium alpha modification -- MH Mueller-Hinton -- MIC minimal inhibitory concentration -- PBP periplasmic-binding protein -- PBS phosphate-buffered saline -- HBTU (2-(1H-benzotriazol-1-yl)-1, 1, 3, 3-tetramethyluronium hexafluorophosphate) -- SPS solid-phase synthesis -- TFA trifluoroacetic acid -- THF tetrahydrofuran -- TIPS triisopropylsilane; Campylobacter jejuni NCTC 11168 -- Gram-negative pathogens -- Iron acquisition -- Siderophore -- Enterobactin -- CfrA -- CeuBCDE -- Solid-phase synthesis; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2018.04.030
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: 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.