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J Libman

Publications and source records attributed to J Libman.

6 recordsLinked to original sources
PubMed1992

Hydrophobic carriers of vanadyl ions augment the insulinomimetic actions of vanadyl ions in rat adipocytes.

A novel family of vanadyl ion (VO2+, oxidation state +4) carriers is introduced. These carriers possess C2 symmetry, utilize two hydroxamate groups as ion binding sites, and optionally possess asymmetric carbons. Binding efficiencies and hydrophobicities are regulated by the use of a modular assembly. When applied to rat adipocytes, these carriers augment the potency of vanadyl ions to stimulate glucose metabolism. The complexes shift the dose-response curve to the left. Also, the maximal effect of vanadyl ions which is in the order of 20-30% of that of insulin is shifted toward maximal (100-115%) stimulation. Among several chelators studied, the order of synergistic potency was RL-252 greater than or equal to RL-262 greater than 1367. RL-239, RL-280, and RL-261 had smaller effects, whereas RL-282 had a negligible effect. The synergistic action of RL-252 (and other chelators as well) on VO2+ was already observed at a molar ratio of 1:0.01 of VO2+ to RL-252, respectively, and maximal augmentation occurred at a molar ratio of 1:0.1. The superiority of the hydrophobic chelators relative to the hydrophilic ones, together with the low molar ratio of chelator to VO2+ to achieve maximal effect, strongly suggests that these chelators act as vanadyl ionophores. This notion was confirmed by carrier-facilitated extraction of VO2+ from water into CHCl3 with the following order of decreasing efficacy: RL-262 greater than RL-252 greater than 1367 greater than RL-261. The chelators' potentiating effect may therefore be related to facilitated transport of VO2+ ions into the cells' interiors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1992

Monitoring of iron(III) removal from biological sources using a fluorescent siderophore.

We present here the physicochemical and biochemical properties of NBD-DFO, the 7-nitrobenz-2-oxa-1,3-diazole (NBD) derivative of the siderophore, desferrioxamine B (DFO) (Lytton et al., Mol. Pharmacol. 40, 584, 1991). Modification of DFO at its terminal amine renders it more lipophilic, imparts to it fluorescent properties, and is conservative of the high-affinity iron(III) binding capacity. NBD-DFO partitions readily from aqueous solution into n-octanol (Pcoeff = 5) and displays solvent-induced shifts in absorption and fluorescence spectra. The relative quantum yield of the probe's fluorescence increases over a 10-fold range with decreasing dielectric constant of the solvent. Fluorescence is quenched upon binding of iron(III) to the probe. We demonstrate here the application of NBD-DFO for the specific detection and monitoring of iron (III) in solutions and iron(III) mobilization from cells. Interactions between fluorescent siderophore and the ferriproteins ferritin and transferrin were monitored under physiological conditions. Iron removal from ferritin was evident by the demonstrable quenching of NBD-DFO fluorescence by scavenged iron(III). Quantitation of iron sequestered from cells by NBD-DFO or from other siderophore-iron(III) complexes was accomplished by dissociation of NBD-DFO-Fe complex by acidification and addition of excess ethylenediamin-etetraacetic acid. The sensitivity of the method and the iron specificity indicate its potential for monitoring chelatable iron under conditions of iron-mediated cell damage, iron overload, and diseases of iron imbalance such as malaria.

4-Chloro-7-nitrobenzofurazan↗
PubMed1992

Iron uptake and molecular recognition in Pseudomonas putida: receptor mapping with ferrichrome and its biomimetic analogs.

The presence of an Fe(3+)-ferrichrome uptake system in fluorescent Pseudomonas spp. was demonstrated, and its structural requirements were mapped in Pseudomonas putida with the help of biomimetic ferrichrome analogs. Growth tests, 55Fe3+ uptake, and competition experiments demonstrated that the synthetic L-alanine derivative B5 inhibits the action of ferrichrome but does not facilitate Fe3+ transport, while the enantiomeric D-Ala derivative B6 fails to compete with ferrichrome. Contraction of the molecule's envelope by replacing L-Ala by glycine provided a synthetic carrier, B9, which fully simulates ferrichrome as a growth promoter. Sodium azide inhibited 55Fe3+ uptake of the Gly derivative B9, suggesting an active transport process. These data demonstrate the chiral discrimination of the ferrichrome receptor and its sensitivity to subtle structural changes. They further confirm that receptor binding is a necessary but not sufficient condition for Fe3+ uptake to occur and suggest that binding to the receptor and transport proteins might rely on different recognition patterns.

Bacterial Outer Membrane Proteins↗
PubMed1991

Chiral linear hydroxamates as biomimetic analogues of ferrioxamine and coprogen and their use in probing siderophore-receptor specificity in bacteria and fungi.

Linear hydroxamate derivatives, possessing chiral alpha-amino acid moieties, were synthesized and their iron transport activities were studied in bacteria and fungi. No growth-promoting activity could be detected in the Gram-positive hydroxamate-auxotroph Aureobacterium flavescens JG9. However, Gram-negative enterobacteria, such as Escherichia coli, Pantoea agglomerans and Hafnia alvei were able to utilize iron from these analogues. Uptake of 55Fe-labeled analogues was inhibited by sodium azide, suggesting an active transport process. The receptors involved during uptake in enterobacteria were identified by using appropriate indicator organisms which are defective in the transport of either ferrioxamines (P. agglomerans FM13), coprogens (H. alvei), or both of these siderophore classes (E. coli fhuE). Our data suggest that the chiral hydroxamates are recognized by the ferrioxamine receptor (FoxA) and the coprogen receptor (FhuE) at a ratio which depends on the optical lambda/delta isomer fraction and the nature of side chains. Transport was also observed in the fungus Neurospora crassa, known to take up coprogen rather than ferrioxamines, suggesting that in this fungus the synthetic analogues behave like coprogen.

Bacteria↗