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I. Fermentation, Isolation and Biological Properties
KEN-ICHI KIMURA, FUMIKO KANOU, HIDETOSHI TAKAHASHI, YASUAKI ESUMI, MAS ...
1997 Volume 50 Issue 5 Pages
373-378
Published: May 25, 1997
Released on J-STAGE: November 25, 2006
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Propeptin, an inhibitor of the prolyl endopeptidase isolated from the mycelium of
Microbispora sp. SNA-115, is an atypical cyclic peptide antibiotic. It was purified by column chromatographies on silica gel and Sephadex LH-20 and high performance liquid chromatography using an ODS column. Propeptin has the molecular formula of C
113H
142N
26O
27 and consists of nineteen amino acids. Propeptin inhibited prolyl endopeptidase of the genus
Flavobacterium competitively when Z-Gly-Pro-ρNA was used as a substrate. The inhibitor constant (
Ki) was 0.70μM.
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I. Screening, Isolation and Structure Elucidation
STEPHAN HEINZE, MICHAEL RITZAU, WOLFGANG IHN, HEIKE HÜLSMANN, BRI ...
1997 Volume 50 Issue 5 Pages
379-383
Published: May 25, 1997
Released on J-STAGE: November 25, 2006
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Lipohexin was isolated as a novel lipohexapeptide (
I) (C
39H
68N
6O
9) from three fungal strains,
Moeszia lindtneri HKI-0054,
Paedlomyces sp. HKI-0055 and
Paedlomyces sp. HKI-0096. The structure was elucidated by detailed mass spectrometric and NMR experiments. The prolinecontaining peptide displays moderate antibacterial activity against
Bacillus subtilis ATCC 6633 and inhibits competitively the prolyl endopeptidase from human placenta.
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II. Inhibitory Activities and Specificity
CLAUDIA CHRISTNER, MARION ZERLIN, UDO GRÄFE, STEPHAN HEINZE, GERH ...
1997 Volume 50 Issue 5 Pages
384-389
Published: May 25, 1997
Released on J-STAGE: November 25, 2006
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The new proline-containing lipohexapeptide lipohexin (
I) isolated from three fungal strains,
Moeszia lindtneri (HKI-0054) and
Paedlomyces sp. (HKI-0055 and HKI-0096) is a competitive inhibitor of prolyl endopeptidase (PEP) from human placenta with IC
50 of 3.5 μM. Specificity of lipohexin (
I) is indicated by the much weaker inhibitory activity against bacterial prolyl endopeptidase from
Flavobacterium meningosepticum (IC
50 25 μM). No effect of lipohexin (
I) was found on the activity of mechanistically related proteases such as proline specific proteases and other serine proteases.
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TATSUO TANIMOTO, KIYOSHI HAMANO, KAORI ONODERA, TSUYOSHI HOSOYA, MAYUM ...
1997 Volume 50 Issue 5 Pages
390-394
Published: May 25, 1997
Released on J-STAGE: November 25, 2006
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Four novel zaragozic acids, F-10863 A, B, C and D, were isolated from a culture broth of the fungus
Mollisia sp. SANK 10294. F-10863 compounds contain a 4, 6, 7-trihydroxy-2, 8-dioxyobicyclo[3.2.1]octane-3, 4, 5-tricarboxylic acid core like previously reported zaragozic acids, but the structures of the side chains are different. Recently, it was found that F-10863 A is identical to zaragozic acid D3, while the other three are novel compounds. F-10863 compounds are potent inhibitors of squalene synthase like previously reported zaragozic acids, and, furthermore, they exhibit serum cholesterol-lowering activity
in vivo.
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ANDREAS FREDENHAGEN, FRANK PETERSEN, MARINA TINTELNOT-BLOMLEY, JOHANNE ...
1997 Volume 50 Issue 5 Pages
395-401
Published: May 25, 1997
Released on J-STAGE: November 25, 2006
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The known bisalkylated 2, 5-dihydroxybenzoquinones didemethylasterriquinone D and iso cochliodinol as well as the new metabolites Semicochliodinol A and B have been isolated as inhibitors of HIV-1 protease from the culture broth of the fungus
Chrysosporium merdarium P-5656. The structures were elucidated by spectroscopic methods. The NMR spectra of two compounds were completely assigned. The metabolites inhibit HIV-1 protease with an IC50 value as low as 0.17 μM and epidermal growth factor receptor protein tyrosine kinase at 15 to 60 μM and are therefore valuable lead compounds for these targets. Molecular modelling of the HIV-1-protease-inhibitor complexes showed hydrogen bonding between the dihydroxybenzoquinone moiety of didemethylasterriquinone D and isocochliodinol to both active-site aspartic acids (Asp25/Asp25') of the protease and the indole parts of the inhibitors filling the P2 and P2' pockets of the protease.
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KAYOKO YAMAJI, MIYAKO MASUBUCHI, FUMIKO KAWAHARA, YUMIKO NAKAMURA, AYA ...
1997 Volume 50 Issue 5 Pages
402-411
Published: May 25, 1997
Released on J-STAGE: November 25, 2006
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DNA gyrase inhibitors, cyclothialidines B, C, D and E were isolated from four Streptomycete strains (NR 0659, NR 0660, NR 0661 and NR 0662). Their structures have been elucidated based on the amino acid analysis of the hydrolysates, NMR and HRFAB-MS experiments and shown to be cyclothialidine analogs. The absolute stereochemistry has been determined by the chiral HPLC analysis of the hydrolysates. Cyclothialidines B, D and E are novel and potent inhibitors of DNA gyrase.
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SUSAN E. LOWE, DONALD R. GUSTAVSON, DAVID S. MEYERS, JUDITH A. VEITCH, ...
1997 Volume 50 Issue 5 Pages
412-417
Published: May 25, 1997
Released on J-STAGE: November 25, 2006
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This paper describes the optimization of production of ascosteroside, a novel antifungal agent with an α-linked glycoside of a lanosterone-type triterpenoid structure. Glucose, sorbose and inositol were determined to be the best carbon sources for the production of ascosteroside. Temperature affected levels of ascosteroside, with production being highest at 16°C with 1% glucose, and lowest at 32°C. Dissolved oxygen levels were found to be critical in the production of ascosteroside in fermenter cultures. In order for production of ascosteroside to occur in fermenter cultures, the threshold level of dissolved oxygen was found to be above 26%.
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ALI SHAFIEE, HAIDEH MOTAMEDI, FRANCIS J. DUMONT, BYRON H. ARISON, RAND ...
1997 Volume 50 Issue 5 Pages
418-423
Published: May 25, 1997
Released on J-STAGE: November 25, 2006
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Two genetically engineered mutant strains of
Streptomyces sp. MA6548 produced two FK506 analogs, 9-deoxo-31-
O-demethylFK506 and 31-
O-demethylFK506. The structures were determined by a combination of NMR and mass spectrometry. These compounds exhibited immunosuppressive and antifungal activities, albeit reduced, compared to FK506. Both compounds contain a free hydroxyl group at C-31 for the synthesis of novel FK506 derivatives.
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FUMITAKA KUDO, NORIAKI YAMAUCHI, RIEKO SUZUKI, KATSUMI KAKINUMA
1997 Volume 50 Issue 5 Pages
424-428
Published: May 25, 1997
Released on J-STAGE: November 25, 2006
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The mechanism of 2-deoxy-
scyllo-inosose synthase reaction, a carbocycle formation step from D-glucose-6-phosphate in the biosynthesis of the 2-deoxystreptamine aglycon of clinically important aminocyclitol antibiotics, was investigated with a partially purified enzyme from butirosin-producing
Bacillus circulans SANK 72073. Nonlabeled and double-labeled D-[4-
2H, 3-
18O]glucose-6-phosphate were used for cross-over experiment, and the oxime-TMS ether derivative of the 2-deoxy-
scyllo-inosose product was analyzed by GC-MS. The deuterium label at C-4 of the substrate appeared to be retained at C-6 of the inosose product without scrambling of the double-labeled isotopes. Since the transient reduction of NAD
+ cofactor was proved to be essential in the 2-deoxy-
scyllo-inosose reaction, the hydride abstraction and returning appeared to take place within the same glucose molecule. The observed kinetic isotope effect was estimated to be k
H/k
D=2.4. These results strongly suggest that this carbocycle formation is catalyzed by a single 2-deoxy-
scyllo-inosose synthase enzyme with catalytic requirement of NAD
+, the mechanism of which appears to be resembled closely to the 2-deoxy-
scyllo-inosose synthase in the
Streptomyces fradiae.
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MASAO MIYAUCHI, ROKURO ENDO, MASAFUMI HISAOKA, HIROSHI YASUDA, ISAO KA ...
1997 Volume 50 Issue 5 Pages
429-439
Published: May 25, 1997
Released on J-STAGE: November 25, 2006
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We have studied an ester prodrug of a carbapenem to develop a potent orally active β-lactam antibiotic. A variety of 1β-methylcarbapenem derivatives have been synthesized. We have found that some derivatives having an amide group in the C-2 side chain show potent and well balanced antibacterial activities as well as high stability against dehydropeptidase-I. Oral absorption of derivatives has been optimized by modifying the C-3 ester promoiety. Pivaloyloxymethyl (1
R, 5
S, 6
S)-6-[(
R)-1-hydroxyethyl]-1-methyl-2-[(
R)-5-oxopyrrolidin-3-ylthio]-1-carbapen-2-em-3-carboxylate, CS-834, has been selected as the most promising compound for further evaluation.
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NORIYUKI YAMASHITA, KAZUO SHIN-YA, MAKOTO KITAMURA, HIROSHI WAKAO, KEI ...
1997 Volume 50 Issue 5 Pages
440-442
Published: May 25, 1997
Released on J-STAGE: November 25, 2006
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FRANK EILBERT, ECKHARD THINES, W. R. ARENDHOLZ, OLOV STERNER, HEIDRUN ...
1997 Volume 50 Issue 5 Pages
443-445
Published: May 25, 1997
Released on J-STAGE: November 25, 2006
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KOZO ODA, TAKAHIDE NISHI
1997 Volume 50 Issue 5 Pages
446-448
Published: May 25, 1997
Released on J-STAGE: November 25, 2006
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HIDEYUKI SHIOZAWA, ATSUKO SHIMADA, SHUJI TAKAHASHI
1997 Volume 50 Issue 5 Pages
449-452
Published: May 25, 1997
Released on J-STAGE: November 25, 2006
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TOSHIAKI SUNAZUKA, TOMOYASU HIROSE, TIAN ZHI-MING, RYUJI UCHIDA, KAZUR ...
1997 Volume 50 Issue 5 Pages
453-455
Published: May 25, 1997
Released on J-STAGE: November 25, 2006
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