The Journal of Antibiotics

STUDIES ON A NEW ANTITUMOR ANTIBIOTIC, LARGOMYCIN. I

TAXONOMY OF THE LARGOMYCIN-PRODUCING STRAIN AND PRODUCTION OF THE ANTIBIOTIC

TOTARO YAMAGUCHI, TAMOTSU FURUMAI, MOTOYOSHI SATO, TOMOHARU OKUDA, NAK ...

1970 Volume 23 Issue 8 Pages 369-372
Published: 1970
Released on J-STAGE: April 12, 2006

DOIhttps://doi.org/10.7164/antibiotics.23.369

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As a result of taxonomic studies on a streptomycete designated MCRL 0367 which produces the antitumor antibiotic largomycin, it was identified as a strain of Streptomyces pluricolorescens OKAMI and UMEZAWA. The production of the Largomycin complex is described.

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STUDIES ON A NEW ANTITUMOR ANTIBIOTIC, LARGOMYCIN. II

ISOLATION, PURIFICATION AND PHYSICOCHEMICAL PROPERTIES

TOTARO YAMAGUCHI, TATSUO KASHIDA, KATSUYUKI NAWA, TAKEHIKO YAJMA, TOSH ...

1970 Volume 23 Issue 8 Pages 373-381
Published: 1970
Released on J-STAGE: April 12, 2006

DOIhttps://doi.org/10.7164/antibiotics.23.373

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Isolation and purification of largomycin from the culture nitrate of Streptomyces pluricolorescens MCRL-0367 is described. The crude complex of largomycin was obtained from the culture nitrate by means of precipitation with ammonium sulfate. Three active components were separated by the following procedures : gradient extraction with aqueous ammonium sulfate solution, isoelectric point precipitation, preparative electrophoresis on polyacrylamide gel, AE-collulose column chromatography, gel-filtration on Sephadex G-100 and dialysis with a cellophane membrane. As a result, the most biologically active component, largomycin F-II, was obtained, the homogeneity of which was proved by ultracentrifugation and electrophoretic analyses. Largomycin F-II proved to be a chromoprotein of high molecular weight (25, 000) containing a pH-indicator chromophore in the molecule. The most unique characteristic of largomycin F-II, which differentiate it from similar antibiotics is the lack of hexosamine and cysteine in its molecule.

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STUDIES ON A NEW ANTITUMOR ANTIBIOTIC, LARGOMYCIN. III

BIOLOGICAL PROPERTIES AND ANTITUMOR ACTIVITY OF LARGOMYCIN F-II

TOTARO YAMAGUCHI, MIKIO SETO, YUKIKO OURA, YOSHIHISA ARAI, KINGO ENOMO ...

1970 Volume 23 Issue 8 Pages 382-387
Published: 1970
Released on J-STAGE: April 12, 2006

DOIhttps://doi.org/10.7164/antibiotics.23.382

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Of the components of largomycin, largomycin F-II was biologically the most active. It is active against Sarcina lutea PCI 1001 at 12.5 mcg/ml, Mycoplasma species at 0.7 mcg/ml and HeLa S-3 cells at 0.1-0.5 mcg/ml. Largomycin F-II exhibited antitumor activity with a chemotherapeutic index of about 100 for ascites tumor and mouse leukemia after 7-day consecutive treatment with 0.4-0.8 mg/kg/day. Against solid tumors, however, largomycin F-II is less active. The high chemotherapeutic index could be explained by its selective toxicity to tumor cells compared with its toxicity to two diploid types of cell of primate origin.

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HODYDAMYCIN, A NEW ANTIBIOTIC

IBRAHIM R. SHIMI, AHMED DEWEDAR, SAFWAT SHOUKRY

1970 Volume 23 Issue 8 Pages 388-393
Published: 1970
Released on J-STAGE: April 12, 2006

DOIhttps://doi.org/10.7164/antibiotics.23.388

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Hodydamycin is a new antibiotic which has been isolated from Streptomyces AS-Y-400 obtained from the soil of Yemen. The antibiotic strongly absorbs iodine and yields five aminoacids on acid hydrolyses. It melts at 145°C and shows an ultraviolet absorption maximum at 249 mμ (E^1%_1cm 358) in neutral and acidic ethanol. Hodydamycin is strictly active against Gram-positive bacteria, possesses low toxicity and markedly high serum binding property.

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BIOLOGICAL STUDIES ON MIKAMYCIN. V

ABSORPTION AND EXCRETION OF TRITIATED MIKAMYCINS A AND B

KIYOSHI WATANABE, KUNIZO YONEZAWA, TOMOYOSHI KOMAI, TOMIO TAKEUCHI

1970 Volume 23 Issue 8 Pages 394-400
Published: 1970
Released on J-STAGE: April 12, 2006

DOIhttps://doi.org/10.7164/antibiotics.23.394

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Mikamycins A & B containing mikamycin A as the main component and mikamycin B as the minor component were tritiated. The ³H-mikamycins A & B were administered orally to mice in four doses of 0.1, 1.0, 10.0 mg/kg/day (for 10 days) and 50 mg/kg (single dose). The amount of ³H-mikamycins A & B excreted into urine and feces was measured daily and totalled, and radioactivity remaining in the mice bodies was determined at intervals after administration ended. Thus, absorption, excretion and a material balance of mikamycins A & B were calculated. At every dose, more than 98% of the radioactivity recovered was excreted in urine and feces within one to several days after administration ended.

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ON THE MODE OF ACTION OF MULTHIOMYCIN

I. EFFECTS OF MULTHIOMYCIN ON MACROMOLECULAR SYNTHESES

TERUO TANAKA, KENJI SAKAGUCHI, HIROSHI YONEHARA

1970 Volume 23 Issue 8 Pages 401-407
Published: 1970
Released on J-STAGE: April 12, 2006

DOIhttps://doi.org/10.7164/antibiotics.23.401

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Muthiomycin, a sulphur-containing antibiotic, inhibited protein synthesis in whole cells of Bacillus subtilis and in Escherichia coli lamelloplast. It did not inhibit transfer of phenylalanine to tRNA or attachment of poly U to ribosomes, and the inhibition of polyphenylalanine synthesis was reversed by increasing amount of ribosomes.

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SYNTHESIS OF MYCOPHENOLIC ACID β-D-GLUCURONIDE AND ITS ANTITUMOR ACTIVITY

KUNIO ANDO, SEIKICHI SUZUKI, MASAHIKO ARITA

1970 Volume 23 Issue 8 Pages 408-413
Published: 1970
Released on J-STAGE: April 12, 2006

DOIhttps://doi.org/10.7164/antibiotics.23.408

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Mycophenolic acid β-D-glucuronide [V] wsa synthesized by KOENIG'S KNORR reaction from methyl mycophenolate [II] and methyl-(tri-O-acetyl-α-D-glucopyranosyl bromide)-uronate [VII]. Hydrolysis of mycophenolic acid β-D-glucuronide by β-glucuronidase liberates mycophenolic acid and glucuronic acid. Upon acid hydrolysis, the T-lactone derivative is formed instead of mycophenolic acid. Mycophenolic acid β-D-glucuronide shows significant antitumor activity against the Ehrlich solid tumor, although it was without effect on nucleic acids synthesis of L-5178 Y cells and the growth of any microorganisms tested. The acute toxicity is very low ; mice tolerate 2, 000 mg/kg intraperitoneal injection.

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POLYENE ANTIBIOTICS. V. CHARACTERIZATION OF COMPONENTS OF THE FILIPIN COMPLEX BY MASS SPECTROMETRY¹⁾

RAMESH G. PANDEY, KENNETH L. RINEHART

1970 Volume 23 Issue 8 Pages 414-417
Published: 1970
Released on J-STAGE: April 12, 2006

DOIhttps://doi.org/10.7164/antibiotics.23.414

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A simple method has been developed for the characterization of neutral polyene antibiotics, involving conversion of the antibiotic to its polyacetate in acetic anhydride-pyridine. Mass spectra of these derivatives contain abundant molecular ions and the number of hydroxyl groups in the antibiotic can be inferred from the number of moles of acetic acid lost. Application of this method to filipins I, II, III and IV assigned them molecular formulas C₃₅H₅₈O₉, C₃₅H₅₈O₁₀, C₃₅H₅₈O₁₁, and C₃₅H₅₈O₁₁, respectively.

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A NEW PEPTIDE ANTIBIOTIC COMPLEX S-520. III

ISOLATION OF L-THREO-β-HYDROXY-GLUTAMIC ACID FROM THE HYDROLYSATE

JUN'ICHI SHOJI, RYUZI SAKAZAKI

1970 Volume 23 Issue 8 Pages 418-419
Published: 1970
Released on J-STAGE: April 12, 2006

DOIhttps://doi.org/10.7164/antibiotics.23.418

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VERTICILLIN A, A NEW ANTI-BIOTIC FROM VERTICILLIUM SF.

KEN KATAGIRI, KOSABURO SATO, SHOHEI HAYAKAWA, TAKASHI MATSUSHIMA, HITO ...

1970 Volume 23 Issue 8 Pages 420-422
Published: 1970
Released on J-STAGE: April 12, 2006

DOIhttps://doi.org/10.7164/antibiotics.23.420

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A NOVEL FATTY ACID FROM LASPARTOMYGIN

HIROSHI NAGANAWA, TOMOHISA TAKITA, KENJI MAEDA, HAMAO UMEZAWA

1970 Volume 23 Issue 8 Pages 423-424
Published: 1970
Released on J-STAGE: April 12, 2006

DOIhttps://doi.org/10.7164/antibiotics.23.423

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GHYMOSTATIN, A NEW GHYMOTRYPSIN INHIBITOR PRODUCED BY ACTINOMYGETES

HAMAO UMEZAWA, TAKAAKI AOYAGI, HAZIME MORISHIMA, SETSUKO KUNIMOTO, MEI ...

1970 Volume 23 Issue 8 Pages 425-427
Published: 1970
Released on J-STAGE: April 12, 2006

DOIhttps://doi.org/10.7164/antibiotics.23.425

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