Synthesis, siderophore activity and iron(III) chelation chemistry of a novel mono-hydroxamate, bis-catecholate siderophore mimic: Nα,-Nε-Bis[2,3-dihydroxybenzoyl]-l-lysyl-(γ-N-methyl-N-hydroxyamido)-l-glutamic acid

Mies, Kassy A.; Gebhardt, Peter; Möllmann, Ute; Crumbliss, Alvin L.

doi:10.1016/j.jinorgbio.2007.11.021

Cited by 12 publications

(7 citation statements)

References 39 publications

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“…Unlike Desferal, but in a similar fashion to enterobactin, 3,4‐LICAMS was able to kinetically mobilize iron from transferrin in vitro, and showed that a rational strategy may be used for the design of ligands with optimal metal chelating properties 335, 338. Research has also focused on the synthesis of mixed‐ligand siderophores, in which at least one chelating moiety is catecholic, for example mono‐catechol bis‐hydroxamate‐339 and bis‐catechol mono‐hydroxamate ligands 339, 340. Other catechol‐based ligands, such as 2,3‐dihydroxyterephtalamide, have been used to prepare pure‐ and mixed‐ligand siderophores with a very high affinity for Fe III , while at the same time being stable to oxidation and presenting low acidity 341.…”

Section: Siderophore‐like Materialsmentioning

confidence: 99%

“…In order to minimize resistance by receptor‐deficient mutants, mixed‐ligand siderophore‐drug conjugates intended to target multiple receptors have been tested, for example carbacephalosporins bearing bis‐catechol‐mono‐hydroxamate hybrid siderophores 377–380. It was suggested that selected mutant strains showing resistance would be, at the same time, severely iron‐deprived for lack of proper iron‐uptake routes, which would make them intrinsically less virulent.…”

Section: Siderophore‐like Materialsmentioning

confidence: 99%

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Catechol‐Based Biomimetic Functional Materials

Saiz‐Poseu²,

et al. 2012

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Abstract.Catechols are found in nature taking part in a remarkably broad scope of biochemical processes and functions. Though not exclusively, such versatility may be traced back to several properties uniquely found together in the o -dihydroxyaryl chemical function; namely, its ability to establish reversible equilibria at moderate redox potentials and pHs and to irreversibly cross-link through complex oxidation mechanisms; its excellent chelating properties, greatly exemplifi ed by, but by no means exclusive, to the binding of Fe 3 + ; and the diverse modes of interaction of the vicinal hydroxyl groups with all kinds of surfaces of remarkably different chemical and physical nature. Thanks to this diversity, catechols can be found either as simple molecular systems, forming part of supramolacular structures, coordinated to different metal ions or as macromolecules mostly arising from polymerization mechanisms through covalent bonds. Such versatility has allowed catechols to participate in several natural processes and functions that range from the adhesive properties of marine organisms to the storage of some transition metal ions. As a result of such an astonishing range of functionalities, catechol-based systems have in recent years been subject to intense research, aimed at mimicking these natural systems in order to develop new functional materials and coatings. A comprehensive review of these studies is discussed in this paper.

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Section: Siderophore‐like Materialsmentioning

confidence: 99%

Section: Siderophore‐like Materialsmentioning

confidence: 99%

Catechol‐Based Biomimetic Functional Materials

Saiz‐Poseu²,

et al. 2012

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“…Growth promotion assays under iron depletion, using a panel of siderophore indicator strains, were applied to demonstrate the recognition of the iron complexes by outer membrane siderophore receptors with a subsequent translocation across the membrane and a release of the iron. (Schumann and Möllmann 2001;Mies et al 2008) The most active siderophore analogues were selected as vectors for the synthesis of drug conjugates.…”

Section: Synthesis and Analysis Of Siderophore Analogs And Their Drugmentioning

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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“…90 In contrast, other siderophore mimics resemble the 'natural' function of siderophores and hence promote bacterial growth by delivering iron ions to these organisms. 91 Jean-Louis Pierre and colleagues have recently reviewed aspects of synthetic siderophore mimics and their potential therapeutic uses. 92,93 The lead structures for iron chelators identified at the time, further developments since then and the design criteria for such oral chelators have recently been reviewed by Robert Hider and colleagues (Fig.…”

Section: Strategies To Lower the Labile Ion Poolsmentioning

confidence: 99%

Metal trafficking: from maintaining the metal homeostasis to future drug design

Doering

Burkholz

et al. 2009

Metallomics

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The diverse proteins and enzymes involved in metal trafficking between and inside human cells form numerous transport networks which are highly specific for each essential metal ion and apoprotein. Individual players include voltage-gated ion channels, import and export proteins, intracellular metal-ion sensors, storage proteins and chaperones. In the case of calcium, iron and copper, some of the most apparent trafficking avenues are now well established in eukaryotes, while others are just emerging (e.g. for zinc, manganese and molybdenum). Chemistry provides an important contribution to many issues surrounding these transport pathways, from metal binding-constants and ion specificity to metal-ion exchange kinetics. Ultimately, a better understanding of these processes opens up opportunities for metal-ion-related therapy, which goes beyond traditional chelate-based metal ion detoxification.

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Synthesis, siderophore activity and iron(III) chelation chemistry of a novel mono-hydroxamate, bis-catecholate siderophore mimic: Nα,-Nε-Bis[2,3-dihydroxybenzoyl]-l-lysyl-(γ-N-methyl-N-hydroxyamido)-l-glutamic acid

Cited by 12 publications

References 39 publications

Catechol‐Based Biomimetic Functional Materials

Catechol‐Based Biomimetic Functional Materials

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

Metal trafficking: from maintaining the metal homeostasis to future drug design

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