title: Modular fluorescent-labeled siderophore analogues.
abstract: Biomimetic analogues 1 of the microbial siderophore (iron carrier) ferrichrome were labeled via piperazine with various fluorescent markers at a site not interfering with iron binding or receptor recognition (compounds 10-12). These iron carriers were built from a tetrahedral carbon symmetrically extended with three strands, each containing an amino acid (G = glycyl, A = alanyl, L = leucyl and P = phenylalanyl) and terminated by a hydroxamic acid, which together define an octahedral iron-binding domain. A fourth exogenous strand provided the site for connecting various fluorescent markers via a short bifunctional linker. Iron(III) titrations, along with fluorescence spectroscopy, generated quenching of fluorescence emission of some of the probes used. The quenching process fits the Perrin model which reinforces the intramolecular quenching process, postulated previously.1 All tested compounds, regardless of their probe size, polarity, or the linker binding them to the siderophore analogue, promote growth of Pseudomonas putida with the same efficacy as the nonlabeled analogues 1, with the added benefit of signaling microbial activity by fluorescence emission. All G derivatives of compounds 10-12 were found to parallel the behavior of natural ferrichrome, whereas A derivatives mediated only a modest iron(III) uptake by P. putida. Incubation of various Pseudomonas strains with iron(III)-loaded G derivatives resulted in the build-up of the labels' fluorescence in the culture medium to a much larger extent than from the corresponding A derivatives. The fluorescence buildup corresponds to iron utilization by the cells and the release of the fluorescent labeled desferrisiderophore from the cell to the media. The fact that the microbial activity of these compounds is not altered by attachment of various fluorescent markers via a bifunctional linker proposes their application as diagnostic tools for detecting and identifying pathogenic microorganisms.
authors.affiliation: Department of Organic Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Nudelman
authors.forename: O
authors.initials: O
authors.lastname: Ardon
authors.forename: Y
authors.initials: Y
authors.lastname: Hadar
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: J
authors.initials: J
authors.lastname: Libman
authors.forename: A
authors.initials: A
authors.lastname: Shanzer
mesh_terms: D015195:Drug Design; D005290:Ferric Compounds / Q000737:chemistry / Q000378:metabolism; D005291:Ferrichrome / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000737:chemistry*; D007502:Iron Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018716:Molecular Mimicry; D016958:Pseudomonas putida / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism
chemical_list: D005290:Ferric Compounds; D005456:Fluorescent Dyes; D007502:Iron Chelating Agents; D005291:Ferrichrome