Konstitution der Desferriform der Albomycine ?1, ?2, ?

Benz, G�nter; Schr�der, Theo; Kurz, Jürgen; W�nsche, Christian; Karl, Wolfgang; Steffens, Gerd; Pfitzner, Jörg; Schmidt, Delf

doi:10.1002/anie.198213220

Cited by 31 publications

(22 citation statements)

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“…The discovery of natural conjugates between siderophores and antibiotics, e.g. the ferrimycins [176], the albomycins [177], the danomycins [178] and the salmycins [179], has led to synthetic analogues. Desferri-ferrioxamin B has been coupled to penicillins [180], cephalosporins [181], sulfonamides [182], and other antibiotics [183].…”

Section: Discussionmentioning

confidence: 99%

Peptide siderophores

1998

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Siderophores are low molecular weight iron chelators, produced by virtually all bacteria, fungi and some plants. They serve to deliver the essential element iron, barely soluble under aerobic conditions, into microbial cells. Siderophores are therefore important secondary metabolites which are very often based on amino acids and their derivatives. Biosynthesis, transport, regulation and chemical synthesis of natural siderophores and their analogues is of considerable interest for the protein and peptide chemist. This review gives an overview of the structural classes of peptidic siderophores, along with data on their biosynthesis. On a number of representative examples, strategies and schemes of their chemical synthesis are described.

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Section: Discussionmentioning

confidence: 99%

Peptide siderophores

1998

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“…Examples of natural siderophore antibiotic conjugates are albomycins, ferrimycins, danomycins, and salmycins, which were isolated mainly from streptomycetes or actinomycetes, and several microcins from enteric bacteria. Albomycins are composed of a tris(N 5 -acetyl, N 5 -hydroxyornithine) peptide and a nucleoside-analogous thioribosyl pyrimidine moiety linked by a serine spacer (17). Because of its similarity to fungal ferrichromes, albomycin is recognized by the FhuA receptor and the FhuD binding protein, which was shown by both mutagenesis (259) and crystallization studies (58).…”

Section: "Trojan Horse" Antibioticsmentioning

confidence: 99%

Siderophore-Based Iron Acquisition and Pathogen Control

Miethke

Marahiel

2007

Microbiol Mol Biol Rev

1,442

1,302

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SUMMARY High-affinity iron acquisition is mediated by siderophore-dependent pathways in the majority of pathogenic and nonpathogenic bacteria and fungi. Considerable progress has been made in characterizing and understanding mechanisms of siderophore synthesis, secretion, iron scavenging, and siderophore-delivered iron uptake and its release. The regulation of siderophore pathways reveals multilayer networks at the transcriptional and posttranscriptional levels. Due to the key role of many siderophores during virulence, coevolution led to sophisticated strategies of siderophore neutralization by mammals and (re)utilization by bacterial pathogens. Surprisingly, hosts also developed essential siderophore-based iron delivery and cell conversion pathways, which are of interest for diagnostic and therapeutic studies. In the last decades, natural and synthetic compounds have gained attention as potential therapeutics for iron-dependent treatment of infections and further diseases. Promising results for pathogen inhibition were obtained with various siderophore-antibiotic conjugates acting as “Trojan horse” toxins and siderophore pathway inhibitors. In this article, general aspects of siderophore-mediated iron acquisition, recent findings regarding iron-related pathogen-host interactions, and current strategies for iron-dependent pathogen control will be reviewed. Further concepts including the inhibition of novel siderophore pathway targets are discussed.

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“…Albomycins are composed of ferrichrome, a tris(N 5 -acetyl, N 5 -hydroxyornithine) peptide, and a nucleoside-analogous thioribosyl pyrimidine moiety linked by a serine spacer (Benz et al 1982;Bickel et al 1965). Ferrimycins are hybrids of ferrioxamine B and an antibiotically active group.…”

Section: Introductionmentioning

confidence: 99%

“…Examples of natural siderophore drug conjugates (SDC) are the sideromycins albomycin, produced by Actinomyces subtropicus (Gause 1955;Benz et al 1982;Fiedler et al 1985), ferrimycins, produced by Streptomyces griseoflavus (Bickel et al 1960(Bickel et al , 1965Sackmann et al 1962) and salmycin, produced by Streptomyces violaceus (Vertesy et al 1995;Pramanik and Braun 2006). Albomycins are composed of ferrichrome, a tris(N 5 -acetyl, N 5 -hydroxyornithine) peptide, and a nucleoside-analogous thioribosyl pyrimidine moiety linked by a serine spacer (Benz et al 1982;Bickel et al 1965).…”

Section: Introductionmentioning

confidence: 99%

Siderophores as drug delivery agents: application of the “Trojan Horse” strategy

et al. 2009

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The outer membrane permeability barrier is an important resistance factor of bacterial pathogens. In combination with drug inactivating enzymes, target alteration and efflux, it can increase resistance dramatically. A strategy to overcome this membrane-mediated resistance is the misuse of bacterial transport systems. Most promising are those for iron transport. They are vital for virulence and survival of bacteria in the infected host, where iron depletion is a defense mechanism against invading pathogens. We synthesized biomimetic siderophores as shuttle vectors for active transport of antibiotics through the bacterial membrane. Structure activity relationship studies resulted in siderophore aminopenicillin conjugates that were highly active against Gram-negative pathogens which play a crucial role in destructive lung infections in cystic fibrosis patients and in severe nosocomial infections. The mechanism of action and the uptake of the compounds via specific iron siderophore transport routes were demonstrated. The novel conjugates were active against systemic Pseudomonas aeruginosa infections in mice with ED(50) values comparable to the quinolone ofloxacin and show low toxicity.

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Konstitution der Desferriform der Albomycine ?1, ?2, ?

Cited by 31 publications

References 10 publications

Peptide siderophores

Peptide siderophores

Siderophore-Based Iron Acquisition and Pathogen Control

Siderophores as drug delivery agents: application of the “Trojan Horse” strategy

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