title: Synthesis, siderophore activity and iron(III) chelation chemistry of a novel mono-hydroxamate, bis-catecholate siderophore mimic: N(alpha),-N(epsilon)-Bis[2,3-dihydroxybenzoyl]-l-lysyl-(gamma-N-methyl-N-hydroxyamido)-L-glutamic acid.
abstract: The synthesis and characterization of a novel tripodal mono-hydroxamate, bis catecholate siderophore mimic, N(alpha),-N(epsilon)-bis[2,3-dihydroxybenzoyl]-l-lysyl-(gamma-N-methyl-N-hydroxyamido)-l-glutamic acid (H(6)L), is described. The structure of H(6)L was established by 2D NMR and mass spectrometry. The chelation chemistry of H(6)L with respect to iron(III) is characterized in aqueous solution through determination of ligand pK(a) values and iron(III) binding constants using spectrophotometric and potentiometric titration techniques. Proton dependent iron(III)-ligand equilibrium constants were determined using a model based on the sequential protonation of the iron(III)-siderophore complex. These results were used to calculate the pH dependent speciation, the overall formation constant logbeta(110) (31.4) and pM value (18.3) for H(6)L with iron(III). The ability of H(6)L to deliver the essential nutrient iron to living cells is determined through growth promotion assays using various bacterial strains.
authors.affiliation: Department of Chemistry, Duke University, P.O. Box 90346 Durham, NC 27708-0346, United States.
authors.forename: Kassy A
authors.initials: KA
authors.lastname: Mies
authors.forename: Peter
authors.initials: P
authors.lastname: Gebhardt
authors.forename: Ute
authors.initials: U
authors.lastname: Möllmann
authors.forename: Alvin L
authors.initials: AL
authors.lastname: Crumbliss
mesh_terms: D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry; D007502:Iron Chelating Agents / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D018716:Molecular Mimicry; D017262:Siderophores / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D004151:Dipeptides; D007502:Iron Chelating Agents; C530572:N(alpha),-N(epsilon)-bis(2,3-dihydroxybenzoyl)-l-lysyl-(gamma-N-methyl-N-hydroxyamido)-L-glutamic acid; D017262:Siderophores