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D L Zink

Publications and source records attributed to D L Zink.

At least 37 records · Page 2Linked to original sources
PubMed1994

Pneumocandin D0, a new antifungal agent and potent inhibitor of Pneumocystis carinii.

Pneumocandin D0 (9), a new member of the echinocandin class of antifungal agents, has been isolated as a minor constituent from fermentation broths of the filamentous fungi Zalerion arboricola (ATCC 20957). The structure of 9 has been determined mainly on the basis of spectroscopic analysis and by comparison with published data for similar compounds. To date, pneumocandin D0 has been found to be the most potent inhibitor of Pneumocystis carinii development in vivo within the natural-occurring echinocandin family of antifungal agents.

Amino Acid Sequence↗
PubMed1993

A light stabilizer (Tinuvin 770) that elutes from polypropylene plastic tubes is a potent L-type Ca(2+)-channel blocker.

A pharmacologically active agent was easily extracted by aqueous or organic solvents from laboratory plastic tubes (Falcon Blue Max) and has been chemically identified as bis(2,2,6,6-tetramethyl-4-piperidyl) sebacate. This compound (approximately 12 micrograms per tube approximately 25 nmol) blocked 1,4-dihydropyridine-sensitive 45Ca2+ uptake into GH3 cells with an IC50 value of 3.6 microM, inhibited Sr2+ currents through L-type Ca2+ channels in A7r5 smooth-muscle cells in whole-cell patch-clamp experiments after extracellular application, and affected the high-affinity binding of Ca2+ entry-blocker ligands to a variety of preparations. Bis(2,2,6,6-tetramethyl-4-piperidyl) sebacate is a highly potent (IC50 values < 10 nM) inhibitor at the phenylalkylamine- and benzothiazepine-selective drug-binding domains of the alpha 1 subunit of L-type Ca2+ channels. This compound behaves as a heterotropic allosteric regulator for the 1,4-dihydropyridine-selective domain in purified Ca(2+)-channel preparations from rabbit skeletal muscle. (+)-Tetrandrine stimulation of 1,4-dihydropyridine binding to the membrane-bound L-type Ca2+ channel is inhibited by the compound in a competitive manner (Ki value = 6.8 nM). Bis(2,2,6,6-tetramethyl-4-piperidyl) sebacate is therefore classified as the prototype of another class of L-type Ca(2+)-channel blockers that binds to the alpha 1 subunit at the drug-binding domains selective for (+)-tetrandrine or (+)-cis-diltiazem. This compound is identical to Tinuvin 770, which is used worldwide as a light stabilizer for polyolefins.

Alkaloids↗
PubMed1993

Zaragozic acids D and D2: potent inhibitors of squalene synthase and of Ras farnesyl-protein transferase.

Two new zaragozic acids, D and D2, have been isolated from the keratinophilic fungus Amauroascus niger. Zaragozic acids D [4] and D2 [5] are related to the previously described zaragozic acids A [1], B [2], and C [3] and are potent inhibitors of squalene synthase. Furthermore, all the zaragozic acids (A, B, C, D, and D2) are also active against farnesyl transferase. Zaragozic acids D and D2 inhibit farnesyl transferase with IC50 values of 100 nM, while zaragozic acids A and B are less potent.

Alkyl and Aryl Transferases↗
PubMed1992

Pneumocandins from Zalerion arboricola. III. Structure elucidation.

Pneumocandin B0 (6) and six related lipopeptides are antifungal and anti-Pneumocystis carinii agents from mutants of Zalerion arboricola, whose structures were determined mainly on the basis of spectroscopic analysis. They belong, along with pneumocandin A0 (L-671,329) previously isolated from these laboratories, to the echinocandin class of antifungal agents. The product from base-catalyzed ring opening involving the hemiaminal position of the dihydroxyornithine residue of B0, has been clearly defined as 6b. Modifications were limited to the 3-hydroxy-4-methylproline, 3,4-dihydroxyhomotyrosine and 4,5-dihydroxyornithine residues of pneumocandin A0.

Anti-Bacterial Agents↗
PubMed1991

Novel and potent gastrin and brain cholecystokinin antagonists from Streptomyces olivaceus. Taxonomy, fermentation, isolation, chemical conversions, and physico-chemical and biochemical properties.

The discovery and physico-chemical characterization of three novel and minor virginiamycin M1 analogs as potent gastrin antagonists from a culture of a strain of Streptomyces olivaceus are described. These analogs are L-156,586, L-156,587 and L-156,588. They are, respectively, 15-dihydro-13,14-anhydro-, 13,14-anhydro- and 13-desoxy-analogs of virginiamycin M1. We also chemically converted virginiamycin M1 (via L-156,587) to L-156,586 and its unnatural epimer, L-156,906. These analogs are competitive and selective antagonists of gastrin and brain cholecystokinin binding at nanomolar concentrations. These are the most potent gastrin/brain cholecystokinin antagonists from natural products. The same compounds showed poor Gram-positive antibiotic activity versus virginiamycin M1. Structurally related Gram-positive antibiotics, griseoviridin and madumycin I, were inactive in gastrin and brain cholecystokinin binding at up to 100 microM.

Animals↗
PubMed1990

Inhibition of human immunodeficiency virus-1 reverse transcriptase activity by rubromycins: competitive interaction at the template.primer site.

Rubromycins, a class of quinone antibacterials, were discovered to selectively inhibit human immunodeficiency virus-1 (HIV-1) RNA-directed DNA polymerase (reverse transcriptase) (RT) activity more potently than cellular DNA polymerase alpha. beta- and gamma-rubromycin each inhibited equipotently HIV-1 RT and avian myeloblastosis virus RT, in a concentration-dependent manner, and were significantly weaker as inhibitors of calf thymus DNA polymerase alpha. These agents inhibited HIV-1 RT reversibly, were competitive with respect to template.primer, and were noncompetitive with respect to TTP. Dixon analyses yielded HIV RT Ki values of 0.27 +/- 0.014 and 0.13 +/- 0.012 microM for beta- and gamma-rubromycin, respectively. Similarly, using DNA polymerase alpha, the Ki values were 25.1 +/- 4.3 and 3.9 +/- 0.6 microM for beta- and gamma-rubromycin, respectively. Because these agents were toxic to noninfected human T lymphoid cells using concentrations at or above 6 microM, HIV-1 infectivity studies were carried out at 0.8-6 microM. At these concentrations, which are below the range expected to provide protection, no significant antiviral activity was observed. Although beta- and gamma-rubromycins did not possess sufficient HIV RT inhibitory potency or selectivity versus mammalian DNA polymerase to demonstrate antiviral activities, these studies support the hypothesis that specific molecules containing quinone functional groups can selectively inhibit viral polymerase activities over cellular polymerase activities. In addition, these studies suggest that rubromycins may be lead structures for the development of more potent and selective agents.

Anti-Bacterial Agents↗
PubMed1985

Corynebacterium pseudotuberculosis exotoxin: fatal hemolytic anemia induced in gnotobiotic neonatal small ruminants by parenteral administration of preparations containing exotoxin.

Inoculation of live Corynebacterium pseudotuberculosis, culture supernatant, ammonium sulfate-fractionated crude exotoxin, or chromatographically purified exotoxin preparations into gnotobiotic small ruminants (n = 13) caused death of the ruminants within 48 hours. Characteristic changes observed in animals living greater than or equal to 2 hours after inoculation included hemorrhage and edema at the site of injection, severe hemolytic anemia and hemoglobinuria, dark red fluid in body cavities, lung edema, and icterus. The crude exotoxin preparation caused a syndrome of acute shock in 2 lambs that died within 15 minutes after inoculation. Clinical and pathologic responses of animals inoculated with culture supernatant and purified toxin were similar. Histopathologic evidence indicated that the exotoxin caused necrotic changes in the proximal convoluted tubules of the kidneys. Inoculation with live organisms caused multiple foci of suppurative inflammation in skeletal muscle and adjacent adipose tissue, whereas such changes were not observed in animals administered exotoxin preparations. Although C pseudotuberculosis exotoxin induced a hemolytic anemia in the experimental animals, it did not lead to in vitro lysis of ovine, caprine, or bovine erythrocytes, unless they had been sensitized with Rhodococcus (Corynebacterium) equi filtrate. The toxic sphingomyelin-specific phospholipase D from C pseudotuberculosis had a molecular weight of 31,000 daltons and an isoelectric point of approximately 9.6. The elution profile of exotoxin on a carboxymethyl Sephadex column was studied and the majority of the enzymatic activity was eluted by a NaCl gradient (0.25M to 0.7M) with a maximum at 0.35M NaCl.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Hemolytic↗
PubMed1984

Plasmid-associated cell surface charge and hydrophobicity of Yersinia enterocolitica.

Virulent strains of Yersinia enterocolitica and their plasmidless, avirulent derivatives were examined for their cell surface properties. Increased surface charge and hydrophobicity of Y. enterocolitica were found to be associated with the possession of a 40- to 48-megadalton plasmid. These surface properties were expressed, as were other plasmid-associated properties, at 37 but not at 22 degrees C. The concentration of calcium in the growth medium had a moderate effect on the expression of the cell surface properties. These cell surface properties were greatly reduced among plasmid-bearing cells grown on tryptic soy agarose regardless of growth temperatures. These properties were also associated with the ability of Y. enterocolitica to colonize the gastrointestinal tract of mice.

Cell Membrane↗
PubMed1984

Association of fibril structure formation with cell surface properties of Yersinia enterocolitica.

Electron microscopic examination of virulence plasmid-bearing cells of Yersinia enterocolitica revealed the formation of a fibril structure when grown at 37 degrees C but not at 22 degrees C. Plasmidless cells did not exhibit any surface matrix. The formation of this surface component was associated with increased cell surface charge and hydrophobicity, formation of long chains of cells, and autoagglutination. This structure is distinct from the rigid appendages (fimbriae) which are elaborated by certain Yersinia strains.

Adhesiveness↗
PubMed1984

Determination of plasmid-associated hydrophobicity of Yersinia enterocolitica by a latex particle agglutination test.

A quick and simple method was developed to distinguish hydrophobic from hydrophilic cells. The latex particle agglutination test is based on the hydrophobic interactions between cells and latex particles which result in the agglutination of the suspension mixture. There was a direct correlation between the expression of plasmid-associated cell surface properties and latex particle agglutination by Yersinia enterocolitica. Multivalent cation-induced agglutination of suspensions of washed cells of virulent Y. enterocolitica and latex particles is indicative of their amphipathic character. Electrostatic interaction may also play a role in the latex particle agglutination reaction.

Latex Fixation Tests↗
PubMed1982

Bacterial antibiotic resistance: frequency of gentamicin-resistant strains of Escherichia coli in the fecal microflora of commercial turkeys.

The relationship of subtherapeutic feeding and parenteral injection of antibiotics to the presence of antibiotic resistant strains of Escherichia coli in the fecal microflora of commercial turkeys has been investigated. Cloacal swabs collected from 137 commercial turkeys were examined for E coli resistant to gentamicin. Gentamicin-resistant E coli organisms were isolated and tested for resistance to ampicillin, chloramphenicol, kanamycin, streptomycin, and tetracycline. Strains of E coli resistant to gentamicin were identified in 118 of 137 (86.1%) specimens evaluated. There were 5 different antibiotic resistance patterns exhibited by the gentamicin-resistant strains of E coli. All strains showed a common antibiotic resistance pattern of gentamicin, kanamycin, and streptomycin. The results of the antibiotic susceptibility tests were compared to the known history of antibiotic usage in each flock. There was no significant correlation between the use of subtherapeutic concentrations of antibiotics and the frequency of gentamicin resistant E coli. However, the frequency of gentamicin-resistant E coli was closely related to the age of the bird, with birds less than 12 weeks of age being most likely to harbor E coli resistant to gentamicin. This age-dependent frequency of gentamicin-resistant E coli was associated with the common practice of dipping eggs in gentamicin and injecting newly hatched poults with gentamicin, but not with the feeding of subtherapeutic concentrations of antibiotics.

Age Factors↗
PubMed1981

Comparison of plasmid deoxyribonucleic acid contents, culture characteristics, and indices of pathogenicity among selected strains of Vibrio parahaemolyticus.

Thirty-one Kanagawa-positive and -negative Vibrio parahaemolyticus isolates from patient stools and seafood were examined for plasmid deoxyribonucleic acid content, culture characteristics, and indices of pathogenicity. No significant correlation was found between plasmid deoxyribonucleic acid contents and indices of pathogenicity for the strains tested.

Anti-Bacterial Agents↗
PubMed1980

Plasmid-mediated tissue invasiveness in Yersinia enterocolitica.

Plasmids have an important role in the pathogenicity of certain bacterial species, and Escherichia coli provides the most complete example of the relationship involved. Enterotoxigenic strains of E. coli, in addition to producing heat-stable and/or heat-labile enterotoxins, may also produce a haemolysin and fimbriate cell surface antigens which facilitate the adherence of the bacterial cell to the mucosa of the small bowel. Numerous studies have shown that these properties are plasmid-mediated and that the plasmids act in concert to confer on the host bacterium the ability to produce enteric disease in man and in animals. Moreover, studies with invasive strains of E. coli have shown that the Col V plasmid, which codes for the synthesis of colicin V, significantly enhances the pathogenicity of its host bacterium. Although the relationship between Col V plasmids and virulence is unclear, reports indicate that Col V-containing strains of E. coli are better able to survive in the alimentary tract and that colicine V itself inhibits macrophage function. It is probable that bacterial virulence is a complex phenomenon involving both chromosomal and plasmid genes. We describe here a virulence plasmid which mediates tissue invasiveness in human pathogenic strains of Yersinia enterocolitica.

Bacterial Toxins↗