The Journal of Antibiotics
Online ISSN : 1881-1469
Print ISSN : 0021-8820
ISSN-L : 0021-8820
Volume 47 , Issue 9
Showing 1-16 articles out of 16 articles from the selected issue
  • TSUTOMU KAMIYAMA, TAKAYUKI UMINO, YUMIKO NAKAMURA, YOSHIKO ITEZONO, SA ...
    1994 Volume 47 Issue 9 Pages 959-968
    Published: September 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Novel thrombin inhibitors, bacithrocins A, B and C, have been isolated from the culture broth of Bacillus laterosporus Laubach NR 2988. The structures of these inhibitors have been determined to be N-acyl-L-phenylalanyl-DL-arginal by the 2D-NMR experiments on their oxidation products and by amino acid analysis. Bacithrocin A inhibits thrombin, factor Xa and trypsin with IC50s of 48, 13 and 0.65μM, respectively, which are similar to those of bacithrocins B and C. Bacithrocins prolong the clotting time induced by thrombin and factor Xa.
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  • II. GENINTHIOCIN, A NOVEL THIOPEPTIDE PRODUCED BY Streptomyces sp. DD84
    BONG-SIK YUN, TOMOMI HIDAKA, KAZUO FURIHATA, HARUO SETO
    1994 Volume 47 Issue 9 Pages 969-975
    Published: September 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Geninthiocin was isolated from the mycelium of Streptomyces sp. DD84 as a tip A promoter inducing substance. Based on various NMR studies, its structure was established as a thiopeptide with oxazole and thiazole moieties, and several unusual amino acids.
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  • AKIO MAEDA, HIROSHI NAGAI, KATSUKIYO YAZAWA, YASUSHI TANAKA, TAMAE IMA ...
    1994 Volume 47 Issue 9 Pages 976-981
    Published: September 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Three new metabolites were isolated from a pathogenic bacterium, Nocardia brasiliensis IFM 0075 strain, a producer of a new anthracycline antibiotic (SO-075R1) and its mutant strain (IFM 0075-13-1). The structural studies showed that they are reduced anthracyline related compounds. Some biosynthetic routes of these matabolites were discussed.
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  • III. FERMENTATION AND CONTROLLED BIOSYNTHESIS OF EURYSTATIN ANALOGS BY Streptomyces eurythermus
    KIYOSHI SUZUKI, SOICHIRO TODA, TAMOTSU FURUMAI, YASUO FUKAGAWA, TOSHIK ...
    1994 Volume 47 Issue 9 Pages 982-991
    Published: September 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Accurate and precise component analysis of eurystatin analogs in fermentation broth was devised by HPLC methods with and without 2, 4-dinitrophenylhydrazonation. Detailed optimization of fermentation conditions and strain improvement by HPLC analysis significantly increased the eurystatin productivity of Streptomyces eurythermus. Chemically denned fermentation media which produced eurystatins A and B at fermentation yields comparable to complex media were elaborated for radio-isotope fermentation studies and controlled biosynthesis. Radio-isotope incorporation study using 14C-labeled amino acids in chemically defined medium demonstrated that L-leucine and L-ornithine were the direct precursors for the L-leucine and L-ornithine moieties of eurystatins A and B, respectively. Based on this finding, L-valine and L-isoleucine were supplemented to the growing culture of S. eurythermus in chemically defined medium, which resulted in the controlled biosynthesis of new eurystatin analogs named eurystatins C, D, E and F.
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  • TIM BUCHAN, CLAUDIA ROACH, CAROLYN RUBY, DEAN TAYLOR, CAROL PREISIG, C ...
    1994 Volume 47 Issue 9 Pages 992-1000
    Published: September 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Thienamycin non-producing mutants of Streptomydes cattleya were identified that displayed a cross-feeding relationship. A diffusible product from one of these mutants (RK-11) resulted in restoration of thienamycin production when fed to cultures of another mutant (RK-4). In vivo radiolabeling experiments were conducted to test whether the RK-11 mutant produced a late biosynthetic intermediate which contained a carbapenem ring and a cysteaminyl and/or a hydroxyethyl side chain. Both [35S]cystine and [methyl-3H]methionine were used to label the RK-11 product which was then fed to RK-4 cultures. None of the thienamycin subsequently produced by RK-4 converter cells was labeled, implying the lack of either side chain of the thienamycin molecule in the RK-11 product. Further stability studies suggested that the RK-11 product does not contain a carbapenem ring. Additional feeding experiments with RK-4 cells also ruled out the possibility that the RK-11 product is a co-factor necessary for thienamycin production. It is concluded that the RK-11 product may regulate expression of the thienamycin gene cluster.
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  • CATHY S. TAFT, CAROL S. ENDERLIN, CLAUDE P. SELITRENNIKOFF
    1994 Volume 47 Issue 9 Pages 1001-1009
    Published: September 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    An in vitro assay for (1, 3)β-glucan synthase activity from the filamentous ascomycete Neurospora crassa, suitable for use as a high throughput screen for enzyme inhibitors is described. Samples were added to 25μl reaction mixtures in 96-well V-bottom microtiter plates and plates incubated at 22°C. Reactions were terminated by the addition of TCA and the contents transferred to a Milliblot D apparatus containing Inotech 201-A glass fiber filters. Filters were washed to remove unincorporated substrate and the amount of 14C-labeled (1, 3)β-glucan formed by each reaction was quantitated using a Phosphorlmager. As little as 50 ng of an inhibitor with a Ki of 4μM was detected by this assay. This assay is rapid and cost effective, permitting its use as a screen to detect compounds that inhibit (1, 3)β-glucan synthase activity.
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  • CHRISTIE BOROS, SEAN M. HAMILTON, BARRY KATZ, PALANIAPPAN KULANTHAIVEL
    1994 Volume 47 Issue 9 Pages 1010-1016
    Published: September 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Recently, we reported the isolation of the potent protein kinase C inhibitor balanol (1) from the fungus Verticillium balanoides. In an earlier study, KÖNIG et al reported the isolation of ophiocordin (3), a structural isomer of 1, from the fungus Cordyceps ophioglossoides. The present study was designed to clarify whether or not balanol and ophiocordin are different compounds. The results indicated that the two fungi produced the same compound, the structure being that assigned to balanol. In addition, a thirty-fold increase in the production of balanol from V. balanoides was observed when the culture medium was changed from cornmeal/tomato paste to soy meal/glycerol.
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  • II. STRUCTURE ELUCIDATION
    ROBERT VELTEN, DÖRTE KLOSTERMEYER, BERT STEFFAN, WOLFGANG STEGLIC ...
    1994 Volume 47 Issue 9 Pages 1017-1024
    Published: September 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The structures of six new drimance sesquiterpenoids, mniopetals A-F, were elucidated by a combination of chemical and spectroscopic methods. The mniopetals are inhibitors of RNA-directed DNA-polymerases.
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  • HIROSHI TANAKA, KAICHIRO KOMINATO, REIKO YAMAMOTO, TAKEO YOSHIOKA, HIR ...
    1994 Volume 47 Issue 9 Pages 1025-1029
    Published: September 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Doxorubicin-γ-cyclodextrin conjugates have been synthesized by the coupling of 14-bromodaunomycin with mono half-ester compounds linked to a 6-hydroxyl group of γ-cyclodextrin. Release of drug from the conjugates in saline phosphate buffer solution and in vitro antitumor activity against L1210 leukemia cells were also investigated.
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  • CHAEUK IM, SAMARENDRA N. MAITI, RONALD G. MICETICH, MOHSEN DANESHXALAB ...
    1994 Volume 47 Issue 9 Pages 1030-1040
    Published: September 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The synthesis of β-lactamase inhibitory activity of a series of sodium 6-[(1-heteroarylthioethyl-1, 2, 3-triazol-4-yl)methylene]pemcillanate 1, 1-dioxides are described. Their activity was compared with tazobactam and sulbactam. The Z-isomers were more active than the E-isomers. The in vitro activity of the Z-isomers of the phenylthiadiazole derivatives (13a and 15a) was better than sulbactam against the tested β-lactamases and comparable to tazobactam especially against TEM-2 and cephalosporinase. But their synergistic activity with five antibiotics was inferior to tazobactam.
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  • SOPHIE VANWETSWINKEL, JACOQUES FASTREZ, JACQUELINE MARCHAND-BRYNAERT
    1994 Volume 47 Issue 9 Pages 1041-1051
    Published: September 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Three new sulfonylamido-penicillanic acid sulfones have been prepared by reaction of 6-aminopenicillanic esters with the monoester or monoamide derivatives obtained in nucleophilic substitution reactions by alcohol or aniline on the carboxyl chloride function of sulfoacetic dichloride followed by oxidation. These penicillin sulfones are converted to βMactamases suicide inhibitors by removal of the C3 ester protecting group. This synthetic strategy can give access to sulfonamido-penam sulfones bearing a variety of 6-amino side chain. These inhibitors inactivate the RTEM βMactamase rapidly. The kinetics of inactivation are consistent with the partitioning of an acyl-enzyme intermediate between two main pathways: regeneration of free enzyme and irreversible inactivation, little transient inactivation is observed. A slow inhibition by the product of enzymatic hydrolysis of the sulfones is also observed.
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  • WILLIAM J. HORNBACK, JOHN E. MUNROE, FRED T. COUNTER
    1994 Volume 47 Issue 9 Pages 1052-1064
    Published: September 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The synthesis and microbiological evaluation of a new series of 3-thiazol-4-yl-carba-1-dethiacephalosporins is described. Structure activity relationship was achieved by changing substitution at the 2-position of the thiazole moiety. The result was a marked variance of microbiological activity in the C7 side-chain derivatives. ATMO derivatives possess potent activity against both Gram-positive and Gram-negative bacteria. For example, MICs (μg/ml) of LY215226 against representative organisms are as follows: S. aureus 0.25, S. pneumoniae 0.008, H. influenzae 0.008, E. coli 0.25, K. pneumoniae 0.008, E. cloacae 0.5, S. typhi 0.25, and M. morganii 0.25.
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  • ATSUKI MORISHITA, SATORU ISHIKAWA, YASUNOBU ITO, KIYOSHI OGAWA, MASAKI ...
    1994 Volume 47 Issue 9 Pages 1065-1068
    Published: September 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • TOMOO KOHYAMA, KEIJI HASUMI, SHIGEO MURAKAWA, AKIRA ENDO
    1994 Volume 47 Issue 9 Pages 1069-1071
    Published: September 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • KAZUTOSHI SHINDO, YUJI YAMAGISHI, YUKIKO OKADA, HIROYUKI KAWAI
    1994 Volume 47 Issue 9 Pages 1072-1074
    Published: September 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • EDWARD KATZ
    1994 Volume 47 Issue 9 Pages 1075-1076
    Published: September 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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