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Biomedical subjects

E Borowski

Publications and source records attributed to E Borowski.

At least 109 records · Page 6Linked to original sources
PubMed1986

Effect of the polar head structure of polyene macrolide antifungal antibiotics on the mode of permeabilization of ergosterol- and cholesterol-containing lipidic vesicles studied by 31P-NMR.

Natural polyene macrolide antibiotics and their N-acyl and methyl ester derivatives, which differ mainly in their electric net charge, were compared for their ability to increase the ionic permeability of large unilamella vesicles, using the proton-cation exchange method and 31P-NMR spectroscopy. The zwitterionic (amphotericin B, vacidin A) and negatively charged (N-N'-diacetyl vacidin) compounds induced permeability according to an all-or-none process on both cholesterol- and ergosterol-containing membranes. The same mechanism of permeability induction is obtained only on ergosterol-containing vesicles for positively charged antibiotics (perimycin A, vacidin A methyl ester, amphotericin B methyl ester). A different type of action is observed for the latter group of ionophores in cholesterol-containing vesicles. In this case, a progressive proton efflux occurs in which all of the vesicle population is involved. This qualitative difference in the kinetics of ionic fluxes induced by antibiotics without a free carboxyl group in cholesterol-containing as compared to ergosterol-containing membranes was ascribed to differences in polyene-sterol interactions as well as in the life time of the ionic path formed. This difference may provide a basis for the improvement of selective toxicity of this group of antifungal agents by rational modifications.

Antifungal Agents↗
PubMed1985

Differential inhibition of DNA and RNA biosynthesis in HeLa S3 cells by tetaine, a dipeptide antibiotic.

A dipeptide antibiotic, tetaine, was found to diminish the rate of incorporation of 3H-labelled precursors into nucleic acids of intact and permeabilized HeLa S3 cells with concomitant negligible effect on protein synthesis. Comparison of the inhibitory effects of tetaine indicates that the antibiotic at 0.03-0.1 mM is a selective inhibitor of cellular DNA biosynthesis and, at higher concentration, of DNA and RNA biosynthesis. Tetaine is also an inhibitor of DNA and RNA polymerase reactions in a cell-free system, as determined using partially purified extracts from HeLa S3 cells that served as a source of the enzymes. The pretreatment experiments showed that tetaine inactivated the polymerases without affecting DNA template function. The tetaine effect on biosynthesis of nucleic acids in HeLa S3 cells can be attributed rather to the intact antibiotic than to the product of its enzymatic cleavage, anticapsin.

Alanine↗
PubMed1985

Synthetic derivatives of N3-fumaroyl-L-2,3-diaminopropanoic acid inactivate glucosamine synthetase from Candida albicans.

Synthetic derivatives of N3-fumaroyl-L-2,3-diaminopropanoic acid constitute the novel group of glutamine analogs. They are powerful, competitive inhibitors of the glucosamine synthetase (2-amino-2-deoxy-D-glucose-6-phosphate ketol-isomerase (amino-transferring), EC 5.3.1.19) from Candida albicans with respect to glutamine and uncompetitive with respect to D-fructose 6-phosphate. Some of the compounds tested irreversibly inactivate glucosamine synthetase with Kinact values of 10(-4) to 10(-6) M. The addition of glutamine protects enzyme from the inactivation, while the absence of D-fructose 6-phosphate lowers the rate of inactivation. An ordered, sequential mechanism is suggested for binding of the inhibitors to the glutamine-binding site. A number of tested compounds act as active-site-directed, irreversible inhibitors. It is suggested that derivatives of N3-fumaroyl-L-2,3-diaminopropanoic acid should be classified as mechanism-based enzyme inactivators. Structural requirements for an effective inactivator containing N3-fumaroyl-L-2,3-diaminopropanoic acid moiety are discussed.

Alanine↗
PubMed1985

The structure of amphotericin A. II. The complete structure of the antibiotic.

The structure of amphotericin A without the configuration of asymmetric carbon atoms has been elucidated. The stereochemistry of the sugar moiety has been determined. On the basis of homoscalar correlated 2D 1H spectra. of amphotericin A the position of the hemiketal moiety has been located, and the chemical shifts of all the protons in the antibiotic molecule have been determined.

Amphotericin B↗
PubMed1984

Inactivation of glucosamine-6-phosphate synthetase from Salmonella typhimurium LT 2 SL 1027 by N beta-fumarylcarboxyamido-L-2,3-diamino-propionic acid.

N beta- fumarylcarboxyamido -L-2,3-diaminopropionic acid ( FCDP ), a novel glutamine analog, inhibits the reaction of glucosamine-6-phosphate synthetase (EC 5.3.1.19) from Salmonella typhimurium LT 2 by irreversible inactivation of the enzyme. The kinetic data on enzyme inhibition and inactivation are presented. It is suggested that the enzyme inactivation occurs according to a sequential mechanism.

Alanine↗
PubMed1984

Potentiation of antiviral activity of acyclovir by polyene macrolide antibiotics.

The potentiation of the antiviral activity of acyclovir [9-[(2-hydroxyethoxy)methyl]guanine] by polyene macrolide antibiotics has been studied as a function of the macrolide structure. The 12 polyenes chosen for this study represented the major structural groups of these antibiotics and induced in mammalian cells repairable membrane alterations or irreversible cell damage. The potentiating activity of the polyene macrolides was determined based on the differential decrease of in vitro production of infectious virions in the presence of acyclovir alone or in combination with the polyene. Pseudorabies virus, a representative herpesvirus susceptible to acyclovir, was replicated in BHK-21 cells grown in serum-free medium to avoid the interference of serum factors in the polyene macrolide-cell interaction. The potentiation activity of the polyene antibiotics was concentration dependent. The enhancement of the antiviral activity of acyclovir was observed at polyene concentrations which had no direct effect on pseudorabies virus replication in BHK-21 cells. The optimal potentiating concentrations of polyenes were 2 to 15 times lower than that inducing 50% of potassium efflux from BHK-21 cells. The highest potentiating activity was observed for the methyl ester of the trimethylammonium derivative of aureofacin B, which reduced the pseudorabies virus titer by two orders of magnitude. Potentiation by polyene macrolides appeared to coincide with the K+-dependent membrane repair process. The acyclovir potentiating activity was associated with polyene macrolide antibiotics having a large and rigid macrolide ring (amphotericin B and aureofacin). Polyene antibiotics with small and rigid (pimaricin and filipin) or large but flexible (nystatin A1 and lienomycin) macrolide rings showed no potentiation of the antiviral effect of acyclovir.

Acyclovir↗
PubMed1984

Anticapsin, an active-site directed irreversible inhibitor of glucosamine-6-phosphate synthetase from Escherichia coli.

Glucosamine-6-phosphate synthetase from Escherichia coli K-12 is progressively inactivated L-beta-(2,3-epoxycyclohexyl-4-on)alanine (anticapsin). With increasing concentrations of anticapsin the reaction exhibits rate saturation: the minimum inactivation half-time is 1.15 minutes, with a Kin alpha ct of 2.5 microM. Glutamine and competitive inhibitors protect against inactivation. Fructose-6-phosphate promotes the inactivation rate. It is concluded that anticapsin is an active-site directed glutamine analog in the reaction catalyzed by glucosamine-6-phosphate synthetase.

Alanine↗
PubMed1984

Inhibition of glucosamine-6-phosphate synthetase from bacteria by anticapsin.

On the basis of kinetic studies on glucosamine-6-phosphate synthetase (EC 5.3.1.19) from six bacteria sources it has been shown that the epoxyamino acid anticapsin, a glutamine analog, is a competitive inhibitor of the enzyme in regard to glutamine with Km value of 10(-4) M and Ki varying from 10(-7) to 10(-6) M. Unlike other glutamine analogs like 6-diazo-5-oxo-L-norleucine, chloropentanoic acid, L-alpha-amino-3-chloro-4,5-dihydro-5-isoxazole acetic acid or albizziin, anticapsin is not generally inhibitory to various amidotransferases. It does not inhibit xanthosine 5'-monophosphate amidotransferase, glutaminase or gamma-glutamyltranspeptidase.

Alanine↗
PubMed1984

The induction of enhanced glucosamine incorporation into the cell-envelope of Escherichia coli K-12 by the antibiotic tetaine.

The dipeptide antibiotic tetaine and its C-terminal aminoacid-anticapsin are powerfull inhibitors of glucosamine-synthetase EC 5.3.1.19 activity in cell-free extract from Escherichia coli K-12. Tetaine strongly inhibits the incorporation of diaminopimelic acid into the peptidoglycan of bacteria. In media with carbon source other than glucose tetaine induced of enhanced glucosamine incorporation into the cell-envelope of Escherichia coli K-12. Compounds from cell-envelope with enhanced labeled glucosamine contents are solubilisable by pronase treatment.

Anti-Bacterial Agents↗
PubMed1983

Circular dichroism study of the interaction between aromatic heptaene antibiotics and small unilamellar vesicles.

Unlike the non-aromatic heptaene amphotericin B, only two types of complex are revealed by circular dichroism when the aromatic heptaenes interact with lipid vesicles. The first is formed when no permeability is observed. The second one is correlated with the appearance of permeability. The cholesterol concentration and the physical state of the membrane have influence only on the amount of the permeabilizing species. These results indicate important differences in the membrane properties of aromatic and non-aromatic heptaenes.

Anti-Bacterial Agents↗
PubMed1983

Growth inhibitory effect of antibiotic tetaine on yeast and mycelial forms of Candida albicans.

The mycelial (M) form of Candida albicans is more sensitive to the action of the antibiotic tetaine than the yeast (Y) form. Tetaine, at low concentrations about 1 microgram/ml also inhibits Y-M transition. It causes severe deformation of cells, agglutination and inhibits septum formation in the yeast forms. Tetaine action is reversed by dipeptides in both forms and by tripeptides in M form. N-acetyl glucosamine is a powerful antagonist of tetaine action on both morphological forms. Tetaine action on mycelial forms is slightly antagonised by N-acetyl mannosamine and very powerfully by glutamine.

Amino Acids↗
PubMed1983

Total synthesis of edeine D.

Syntheses of the peptides with sequences postulated for active and inactive isomer of edeine D were carried out. The peptides obtained were identical with natural product in regard to chromatographic and electrophoretic properties. Biological data for synthesized compounds confirmed that in active and inactive isomer isoserine is linked with the alpha- or beta-amino group of alpha, beta-diaminopropionic acid, respectively.

Anti-Bacterial Agents↗