| 1490877 |
Pneumocandins from Zalerion arboricola. II. Modification of product spectrum by mutation and medium manipulation |
10.7164/antibiotics.45.1867. |
J Antibiot (Tokyo) |
Pneumocandins from Zalerion arboricola. II. Modification of product spectrum by mutation and medium manipulation
Abstract
- Zalerion arboricola ATCC 20868 produces pneumocandin A0 (L-671,329), a cyclic hexapeptide with a dimethylmyristic acid side chain. This compound has anti-candida and anti-pneumocystis activities. We were interested in looking for other related compounds produced by this organism. To facilitate this search, a simple medium (S2) composed of D-mannitol, peptonized milk, lactic acid, glycine, KH2PO4 and trace elements, which supported the production of a number of such compounds, was designed. For the isolation of mutants, either spores or growing mycelia were treated with N-nitroso-N-methylurethane or N-methyl-N'-nitro-N-nitrosoguanidine and survivors were screened for changes in the product spectrum. From approximately 1,500 survivors tested, 5 mutants were isolated. Mutants ATCC 20957, 74030, 20958 and 20988 exclusively produce various pneumocandins other than A0. These compounds were active against Candida and Pneumocystis carinii. The yield of A0 was found to be increased 2.5-fold over that of the parent in the fifth mutant, MF5415. Further medium studies indicated that the addition of soybean oil to S2 medium improved the yields. Subsequent development of another series of media containing Pharmamedia as a nitrogen source resulted in increase in production by 10- approximately 20-fold. Overall, these studies resulted in substantial improvement in the production of A0 as well as discovery and/or facile production of 7 other related compounds."
|
| 1490878 |
Pneumocandins from Zalerion arboricola. III. Structure elucidation |
10.7164/antibiotics.45.1875. |
J Antibiot (Tokyo) |
Pneumocandins from Zalerion arboricola. III. Structure elucidation
Abstract
- 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.
|
| 1490908 |
Antibacterial spectrum of lactoferricin B, a potent bactericidal peptide derived from the N-terminal region of bovine lactoferrin |
10.1111/j.1365-2672.1992.tb05007.x. |
J Appl Bacteriol |
Antibacterial spectrum of lactoferricin B, a potent bactericidal peptide derived from the N-terminal region of bovine lactoferrin
Abstract
- A physiologically diverse range of Gram-positive and Gram-negative bacteria was found to be susceptible to inhibition and inactivation by lactoferricin B, a peptide produced by gastric pepsin digestion of bovine lactoferrin. The list of susceptible organisms includes Escherichia coli, Salmonella enteritidis, Klebsiella pneumoniae, Proteus vulgaris, Yersinia enterocolitica, Pseudomonas aeruginosa, Campylobacter jejuni, Staphylococcus aureus, Streptococcus mutans, Corynebacterium diphtheriae, Listeria monocytogenes and Clostridium perfringens. Concentrations of lactoferricin B required to cause complete inhibition of growth varied within the range of 0.3 to 150 micrograms/ml, depending on the strain and the culture medium used. The peptide showed activity against E. coli O111 over the range of pH 5.5 to 7.5 and was most effective under slightly alkaline conditions. Its antibacterial effectiveness was reduced in the presence of Na+, K+, Mg2+ or Ca2+ ions, or in the presence of various buffer salts. Lactoferricin B was lethal, causing a rapid loss of colony-forming capability in most of the species tested. Pseudomonas fluorescens, Enterococcus faecalis and Bifidobacterium bifidum strains were highly resistant to this peptide.
|
| 1492361 |
Immunomodulatory properties of cyclic hexapeptide oxytocin antagonists |
None |
Thymus |
Immunomodulatory properties of cyclic hexapeptide oxytocin antagonists
Abstract
- The thymic repertoire of neuroendocrine 'self' antigens has been previously described on the basis of the intrathymic expression of neurohypophysial (NHP)- and tachykinin-related peptide signals and receptors. According to that model, the cryptocrine signalling between thymic epithelial/nurse cells and thymocytes through NHP-related signals and receptors constitutes one accessory pathway in the process of T-cell differentiation and/or activation. A pharmacological manipulation of that novel type of cell-to-cell signalling was tested by the investigation of the immunomodulatory properties of novel cyclic hexapeptide oxytocin (OT) antagonists (MSD Research Laboratories). These compounds were found to significantly inhibit the productions of cytokines (mainly IL-1 beta and IL-6) elicited by anti-CD3 treatment of human whole blood cell cultures. Cytokine productions were more significantly reduced by OT antagonists in whole blood cell cultures derived from female volunteers than in those obtained from male donors, suggesting an influence of the gonadal steroid environment on the expression of NHP peptide receptors by immune cells. These observations support the concept of novel immunomodulating approaches through immune-specific neuropeptide antagonists, as well as the pharmacological value of such strategies in selective immunotherapy."
|
| 1494502 |
Immunosuppressive activity of antamanide and some of its analogues |
10.1016/0196-9781(92)90034-z. |
Peptides |
Immunosuppressive activity of antamanide and some of its analogues
Abstract
- In connection with our discovery of a strong immunosuppressive activity of cyclolinopeptide A (CLA), we investigated immunosuppressive properties of antamanide and a number of its analogues, including symmetrical antamanide, and compared them with the activities of cyclosporin A and CLA. The peptides were investigated by using plaque forming cell (PFC), graft-versus-host (GvH), delayed type hypersensitivity (DTH), and autologous rosette formation cell (ARFC) tests. Antamanide and symmetrical antamanide exhibit an immunosuppressive activity lower than CLA. Linear antamanide fragments are also active. At higher concentrations of the latter peptides, toxic effects occur.
|
| 1494575 |
Hepatotoxicity of cyclochlorotine--a cyclic peptide produced by Penicillium islandicum |
None |
Prikl Biokhim Mikrobiol |
Hepatotoxicity of cyclochlorotine--a cyclic peptide produced by Penicillium islandicum
Abstract
- Toxicological investigations of "Yellow Rice" which have been contaminated with various Penicillium species have shown that Penicillium islandicum apart from well-known hepatotoxic mycotoxin, lyteoskyrin synthesizes cyclochlorotine (chloropeptide, CP), which is also hepatotoxic. Isolation of chloropeptide and its chemical characteristics, acute toxicity and biochemical alterations, tissue distribution and excretion, deformation of hepatic cells, and interaction with cytoskeleton filaments are described. It is shown that the hepatotoxicity of CP is inactivated by dehalogenation of CP by the cytochrome P-450 system.
|
| 1496014 |
Conformation for a beta-cyclodextrin monosubstituted with a cyclic dipeptide |
10.1073/pnas.89.15.7218. |
Proc Natl Acad Sci U S A |
Conformation for a beta-cyclodextrin monosubstituted with a cyclic dipeptide
Abstract
- The structural characterization of a beta-cyclodextrin monosubstituted with the peptide cyclo(L-His-L-Leu) is reported. This work provides an x-ray example of a covalently bound group that folds in such a way that the terminal apolar side chain is retained in the hydrophobic interior of the cone-shaped cyclodextrin cavity. 6-Deoxy-6-cyclo(L-histidyl-L-leucyl)-beta-cyclodextrin crystallizes in the space group P1 with cell dimensions a = 14.728(8) A, b = 15.084(7) A, c = 18.182(10) A, alpha = 94.36(6) degrees, beta = 95.81(5) degrees, gamma = 116.08(9) degrees; overall isotropic agreement R = 10.6% for 5703 observed reflections (Fo greater than 3 sigma). The molecular structure consists of two independent molecules with the formula C54H86N4O36.7.25H2O. Each molecule assumes a "sleeping swan"-like overall shape with the hydrophobic leucine side chain inserted inside the cavity of the macrocycle. The two independent units give rise to a head-to-tail dimer linked by hydrogen bonds occurring between primary and secondary hydroxyl groups of the two monomers. The packing of the dimers produces cavities containing water molecules. There are infinite hydrophilic channels running in the crystal, which is similar to what is found in the structures of cyclic peptides.
|
| 1496685 |
Toxicologic evaluation of the new cyclosporin derivative, SDZ IMM 125, in a comparative, subchronic toxicity study in rats |
None |
Transplant Proc |
Toxicologic evaluation of the new cyclosporin derivative, SDZ IMM 125, in a comparative, subchronic toxicity study in rats
Abstract
|
| 1500163 |
Cryptdins: antimicrobial defensins of the murine small intestine |
10.1128/iai.60.9.3556-3565.1992. |
Infect Immun |
Cryptdins: antimicrobial defensins of the murine small intestine
Abstract
- Paneth cells are specialized small intestine epithelial cells that contain lysozyme, possess phagocytic properties, and secrete cytoplasmic granules into the intestinal crypt lumen after the entry of bacteria. Recent studies by Ouellette and associates (A. J. Ouellette, R. M. Greco, M. James, D. Frederick, J. Naftilan, and J. T. Fallon, J. Cell Biol. 108:1687-1695, 1989) indicated that murine Paneth cells produce prodefensin mRNA, but the properties of its peptide product were not reported. We purified two closely related defensins, cryptdin 1 and cryptdin 2, from a subcellular fraction of murine small intestine cells that was enriched in Paneth cells. Both peptides contained 35 amino acid residues, including the characteristic defensin "signature" of six invariantly conserved cysteines. Cryptdins 1 and 2 were approximately 90 to 95% homologous to each other and to the carboxy-terminal domain of the 93-amino-acid defensin precursor, cryptdin A, described by Ouellette and associates (Ouellette et al., J. Cell Biol. 108:1687-1695, 1989). Both cryptdins exerted bactericidal activity against Listeria monocytogenes EGD and Escherichia coli ML-35p in vitro. Their potency exceeded that of human neutrophil defensin HNP-1 but was considerably lower than that of NP-1, a defensin produced by rabbit neutrophils and alveolar macrophages. Both cryptdins killed mouse-avirulent Salmonella typhimurium 7953S (phoP) much more effectively than its phoP+, mouse-virulent, isogenic counterpart, S. typhimurium 14028S. Our data indicate that mouse intestinal prodefensins are processed into 35-amino-acid mature defensins (cryptdins) with broad-spectrum antimicrobial properties. The production of defensins and lysozyme by Paneth cells may enable them to protect the small intestine from bacterial overgrowth by autochthonous flora and from invasion by potential pathogens that cause infection via the peroral route, such as L. monocytogenes and Salmonella species.
|
| 1500346 |
Structures of new peptide antibiotics, plusbacins A1-A4 and B1-B4 |
10.7164/antibiotics.45.824. |
J Antibiot (Tokyo) |
Structures of new peptide antibiotics, plusbacins A1-A4 and B1-B4
Abstract
- The constituent amino acids of plusbacins A1-A4 were determined to be two moles of L-trans-3-hydroxyproline and one mole each of D-threo-beta-hydroxyaspartic acid, L-threo-beta-hydroxyaspartic acid, D-allo-threonine, D-serine, D-alanine and L-arginine. In plusbacins B1-B4, one mole of L-trans-3-hydroxyproline is replaced by L-proline. The fatty acid residue of A1 and B1 was determined to be 3-hydroxy-tetradecanoic acid, for A2 and B2 to be 3-hydroxy-isopentadecanoic acid, for A3 and B3 to be 3-hydroxy-isohexadecanoic acid, and for A4 and B4 to be 3-hydroxy-hexadecanoic acid. A lactone linkage was suggested to reside between L-threo-beta-hydroxyaspartic acid and 3-hydroxy-fatty acid residues by degradation experiments. The amino acid sequences of plusbacins A2 and B2 were confirmed by Edman degradation of their deacylated products, and supported by mass spectrometric studies. From the above, structures of all components of plusbacins were concluded.
|
| 1500431 |
Enteric defensins: antibiotic peptide components of intestinal host defense |
10.1083/jcb.118.4.929. |
J Cell Biol |
Enteric defensins: antibiotic peptide components of intestinal host defense
Abstract
- Five intestinal defensins, termed cryptdins 1-5, have been purified from mouse small bowel, sequenced, and localized to the epithelium by immunohistochemistry. Although identified as members of the defensin peptide family by peptide sequencing, enteric defensins are novel in that four cryptdins have amino termini which are three to six residues longer than those of leukocyte-derived defensins. A fifth cryptdin is the first defensin to diverge from the previously invariant spacing of cysteines in the peptide structure. The most abundant enteric defensin, cryptdin-1, had antimicrobial activity against an attenuated phoP mutant of Salmonella typhimurium but was not active against the virulent wild-type parent. Immunohistochemical localization demonstrated that cryptdin-1, and probably cryptdins 2 and 3, occur exclusively in Paneth cells, where the peptides appear to be associated with cytoplasmic granules. Biochemical and immunologic analysis of the luminal contents of the small intestine suggest that cryptdin peptides are secreted into the lumen, similar to Paneth cell secretion of lysozyme. The presence of several enteric defensins in the intestinal epithelium, evidence of their presence in the lumen, and the antibacterial activity of cryptdin-1 suggest that these peptides contribute to the antimicrobial barrier function of the small bowel mucosa.
|
| 1503503 |
Effect of cyclosporins A, G, and H on normal and ichthyotic keratinocyte growth in culture |
10.1007/BF00372712. |
Arch Dermatol Res |
Effect of cyclosporins A, G, and H on normal and ichthyotic keratinocyte growth in culture
Abstract
- Cyclosporin A (CsA) was first used in organ transplantation and for the treatment of autoimmune disorders because of its strong immunosuppressant properties. Several laboratory studies have demonstrated that CsA exerts an inhibitory action on the growth of various cell types in culture, including human skin cells. Such an influence on epidermal keratinocytes, if not associated with the serious adverse effects of CsA medication, would be of interest for the treatment of hyperproliferative genodermatoses such as non-bullous congenital ichthyotic erythroderma (NBCIE). In our study, we used cyclosporin G (CsG) and H (CsH), analogues CsA, to examine the impact of these three cyclosporins on normal and ichthyotic keratinocyte growth in vitro. Epidermal cells were grown in a low-calcium, serum-free medium in the presence or absence of cyclosporins A, G or H (1-10 micrograms/ml). The effects of a 72-h exposure to the drugs were evaluated by cell counting, 3H-thymidine incorporation and cytofluorimetric analysis of the BrdU-labelled cell suspensions. Our findings indicate a dose-dependent keratinocyte growth inhibition by the three cyclosporins. The data obtained with the three quantitation methods were in agreement and the cyclosporin-mediated effects were observed in both normal and ichthyotic keratinocyte cultures. CsG and CsH proved less effective than CsA, which induced a highly significant reduction even at 1 microgram/ml. Our results suggest, however, that ichthyotic keratinocytes are more sensitive to CsG and H when compared with normal cells (50% inhibition of 3H-thymidine uptake at significantly lower doses). A possible therapeutic action of non-toxic doses of CsG and CsH on NBCIE and other hyperproliferative epidermal diseases needs to be confirmed clinically.
|
| 1506265 |
A novel tetracyclic peptide, trapoxin, induces phenotypic change from transformed to normal in sis-oncogene-transformed NIH3T3 cells |
10.1111/j.1349-7006.1992.tb00109.x. |
Jpn J Cancer Res |
A novel tetracyclic peptide, trapoxin, induces phenotypic change from transformed to normal in sis-oncogene-transformed NIH3T3 cells
Abstract
- A novel tetracyclic peptide, trapoxin cyclo(L-phenylalanyl-L-phenylalanyl-D-pipecolinyl-L-2-amino-8-oxo -9,10-epoxy - decanoyl), was found to induce the flat phenotype in v-sis-transformed NIH3T3 cells at a quite low concentration of 1 ng/ml. Actin stress fiber could be detected after trapoxin treatment. Almost complete reversion into the flat phenotype was observed at 6 h after the administration of the compound. The effect of trapoxin was reversible, when the cell culture was incubated for more than 24 h after its removal. The intracellular level of sis-mRNA did not decrease with trapoxin treatment at a concentration (50 ng/ml), sufficient to reverse the transformed morphology. Substitution of pipecolinic acid with proline in trapoxin did not change the activity. WF3161, in which leucine was substituted for a phenylalanine of trapoxin, showed only one-sixteenth of the activity of trapoxin. Reduction of the epoxide residue of trapoxin destroyed the activity.
|
| 1509499 |
Effect of the cyanobacterial (blue-green algal) toxins from Microcystis aeruginosa on isolated enterocytes from the chicken small intestine |
10.1016/0041-0101(92)90016-x. |
Toxicon |
Effect of the cyanobacterial (blue-green algal) toxins from Microcystis aeruginosa on isolated enterocytes from the chicken small intestine
Abstract
- Livestock deaths, and clinical reports of human injury, follow the consumption of toxic blue-green algae. The experiments described show that isolated intestinal enterocytes from chicks are both deformed and killed by exposure to Microcystis toxins, in a dose-dependent and time-dependent manner. The enterocytes were protected from toxicity by deoxycholate, bromosulphothalein and rifampicin. It was concluded that the gastroenteritis clinically associated with accidental Microcystis ingestion is likely to reflect enterocyte injury by Microcystis toxins, and that the therapeutic use of bile acids or transport inhibitors may be of value in treatment.
|
| 1514796 |
Isolation and characterization of a variety of microcystins from seven strains of the cyanobacterial genus Anabaena |
10.1128/aem.58.8.2495-2500.1992. |
Appl Environ Microbiol |
Isolation and characterization of a variety of microcystins from seven strains of the cyanobacterial genus Anabaena
Abstract
- Hepatotoxins (microcystins) from seven freshwater Anabaena strains originating from three different Finnish lakes and one lake in Norway were isolated by high-performance liquid chromatography and characterized by amino acid analysis and fast atom bombardment mass spectrometry. All strains produced three to seven different microcystins. A total of 17 different compounds were isolated, of which 8 were known microcystins. The known compounds identified from six strains were MCYST (microcystin)-LR, D-Asp3MCYST-LR, Dha7MCYST-LR, D-Asp3,Dha7MCYST-LR, MCYST-RR, D-Asp3MCYST-RR, Dha7MCYST-RR, and D-Asp3,Dha7MCYST-RR. With the exception of MCYST-LR and D-Asp3MCYST-LR, this is the first time that isolation of these toxins from Anabaena strains has been reported. Three of the strains produced one to three toxins as minor components which could not be identified. Anabaena sp. strain 66 produced four unidentified toxins. The other Anabaena strains always contained both MCYST-LR and MCYST-RR and/or their demethyl variants. Quantitative differences between toxins within and between strains were detected; at times MCYST-LR and at other times MCYST-RR or demethyl derivatives thereof were the most abundant toxins found in a strain.
|
