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I. PRODUCTION, ISOLATION AND PROPERTIES
HIROSHI KAWAGUCHI, HIROSHI TSUKIURA, KOJI TOMITA, MASATAKA KONISHI, KY ...
1977 Volume 30 Issue 10 Pages
779-788
Published: 1977
Released on J-STAGE: April 12, 2006
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The unusual actinomycetes strain No. E465-94 produced a complex of new glycopeptide antibiotics tallysomycin, which was separated by CM-Sephadex chromatography into two major components, A (C
68H
107N
21O
27S
2) and B (C
62H
95N
19O
26S
2). They were isolated first in a copperchelated form and showed physico-chemical properties similar to those of the bleomycingroup of antibiotics. Tallysomycin exhibited broad antibacterial and antifungal activity, and was highly active
in vivo against bacterial infections in mice. Tallysomycins A and B demonstrated potent activity in the prophage induction of lysogenic bacteria.
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II. STRUCTURE DETERMINATION OF TALLYSOMYCINS A AND B
MASATAKA KONISHI, KYO-ICHIRO SAITO, KEI-ICHI NUMATA, TAKASHI TSUNO, KO ...
1977 Volume 30 Issue 10 Pages
789-805
Published: 1977
Released on J-STAGE: April 12, 2006
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The structures of tallysomycins A and B, two major components of a new antitumor antibiotic complex, have been determined. They are glycopeptide antibiotics structurally related to bleomycin: four amino acid moieties and a disaccharide fragment which are the constituents of bleomycin molecule are also present in the tallysomycins. Tallysomycins A and B contain two new amino acids and a unique amino sugar, 4-amino-4, 6-dideoxy-L-talose, which
have not been hitherto found in the phleomycin-bleomycin group of antibiotics. In addition tallysomycin A has an additional amino acid, L-β-lysine, and thus a longer peptide chain than bleomycin or tallysomycin B. Tallysomycins A and B have the same terminal amine moiety, spermidine.
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T. ANKE, F. OBERWINKLER, W. STEGLICH, G. SCHRAMM
1977 Volume 30 Issue 10 Pages
806-810
Published: 1977
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The strobilurins are two antifungal antibiotics which were isolated from the mycelium of
Strobilurus tenacellus strain No. 21602. The strobilurins A and B are highly active against yeasts and filamentous fungi.
In vitro antitumor activity was tested using cells of the ascitic
form of EHRLICH carcinoma. The strobilurins strongly inhibited the incorporation of radioactive leucine, uridine, and thymidine into the acid-insoluble fraction of cells (protein, RNA, and DNA). The molecular formulas as determined by high resolution mass spectrometry are C
16H
18O
3 for strobilurin A and C
17H
19ClO
4 for strobilurin B.
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II. USE OF HIGH EFFICIENCY SMALL PARTICLE COLUMNS
E. RODERICK WHITE, MARGARET A. CARROLL, JOHN E. ZAREMBO
1977 Volume 30 Issue 10 Pages
811-818
Published: 1977
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Improved methods for the separation and quantitation of cephalosporins, penicillins, tetracyclines and several miscellaneous antibiotics by reverse phase high speed liquid chromatography are presented. The methods have been improved significant]y by the substitution of high efficiency, small particle (-10μm) reverse phase columns in place of the previously used medium efficiency, pellicular columns. The conditions and procedures described here illustrate that considerable improvements in separation and sensitivity of detection of antibiotics are achieved. Pure compounds, complex mixtures of antibiotics in a variety of dosage forms and fermentation broths are routinely analyzed by the described procedures.
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THE ARTIFACTS AND THE DEGRADATION PRODUCTS OF LYSOCELLIN
MITSUO KOENUMA, NOBORU OTAKE
1977 Volume 30 Issue 10 Pages
819-828
Published: 1977
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Lysocellin is a new polyether antibiotic produced by
Streptomyces cacaoi var.
asoensis and is characterized as a broad spectrum ionophore having a higher complexation affinity for divalent cations than for monovalents and also having an ability to transport biological amines.
The structures of two artifacts designated L
1 and M
1 have been elucidated based on spectral evidence, and the formation mechanism of these compounds was discussed with respect to the reactivity of the antibiotic. In addition, a number of degradation and modified products were prepared in order to examine their biological activity and to utilize as the model compounds for
13C-NMR assignment.
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EFFECTS OF IONOPHORE LYSOCELLIN ON CATION DISTRIBUTION AND RESPIRATION IN MITOCHONDRIA
MITSUAKI MITANI, MITSUO KOENUMA, NOBORU OTAKE
1977 Volume 30 Issue 10 Pages
829-835
Published: 1977
Released on J-STAGE: April 12, 2006
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The effects of the ionophore lysocellin on the movements of Ca
2+, Mg
2+ and alkali metal cations and its effect on energy utilization by rat liver mitochondria have been investigated. At a concentration of 0.05 μM, lysocellin induced dissociation of membrane-bound calcium,
and an apparent steady state was established across the inner membrane between energylinked calcium accumulation and the ionophore-induced depletion of calcium. No detectable efflux of intramitochondrial Ca
2+ and Mg
2+ was induced by 0.05 μM lysocellin, but the uptake of exogenously added calcium was significantly inhibited. The ionophore augmented Mg
2+ release from mitochondria induced by Ca
2+ addition and also caused rapid release of K
+ from mitochondria preloaded with K
+ by valinomycin or monazomycin. High levels (0.5-10 μM) of lysocellin caused massive depletion of endogenous Ca
2+, Mg
2+ and K
+ from mitochondria, resulting in disruption of mitochondrial functions including release of state 4 respiration, stimulation of ATPase and inhibition of ADP- or DNP-stimulated respiration. Structureactivity studies with chemically modified compounds of lysocellin indicated the important role of terminal carboxylic acid and C
21 hydroxyl function in the activity of the ionophore, and there is a good correlation between the effect of lysocellin on mitochondrial cation movements
and its ability to complex with cations determined in an organic solvent-water two-phase partition system.
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I. SYNTHESIS AND BIOLOGICAL EVALUATION OF AN ANALOG OF GENTAMICIN
ROBERT D. SITRIN, DAVID J. COOPER, JERRY A. WEISBACH
1977 Volume 30 Issue 10 Pages
836-842
Published: 1977
Released on J-STAGE: April 12, 2006
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The synthesis of 2-deoxy-4-O-(2, 6-diamino-2, 3, 4, 6-tetradeoxy-α-D-erythrohexopyranosyl)-6-O-(3-deoxy-3-methylamino-α-D-xylopyranosyl)-D-streptamine (
1), an analog of gentamicin A, from dideoxyneamine and methyl 3-methylamino-3-deoxy-β-D-xylopyranoside is described. The product was characterized by its
13C nmr spectrum and was found to exhibit broad spectrum antibacterial activity.
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K. RICHARDSON, S. JEVONS, J. W. MOORE, B. C. Ross, J. R. WRIGHT
1977 Volume 30 Issue 10 Pages
843-846
Published: 1977
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Four 1-N-aminohydroxy-alkyl derivatives of kanamycin A were prepared and their
in vitro activities against aminoglycoside-sensitive and aminoglycoside-resistant organisms were compared with amikacin. 1-N-[(S)-4-Amino-2-hydroxybutyl] kanamycin A (Fig. 1, compound
2, code no. UK-18, 892) was equipotent to amikacin in all these tests and in mouse protection studies.
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E. ROETS, A. VLIETINCK, H. VANDERHAEGHE
1977 Volume 30 Issue 10 Pages
847-855
Published: 1977
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The preparation 6-epi-ampicillin by hydrolysis of 6-epihetacillin is described. During this conversion, the formation of a diketopiperazine was also observed. The best yield was obtained at pH 7.0 and room temperature for 3-7 hours. The lowest yield of 6-epi-ampicillin and the highest formation of the diketopiperazine occurred in pyridine-acetic acid-water. Treatment of ampicillin (with D-aminophenylacetyl side chain) with nitrous acid gave α-hydroxybenzylpenicillin with about 66% of L- and 34% mandelyl side chain. Reaction 6-epi-ampicillin gave 6-epi- α-hydroxybenzylpenicillin with practically the same ratio of L- and D-isomers.
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MIKLOS BODANSZKY, JILL B. HENES, SESHA NATARAJAN, RODGER L. FOLTZ
1977 Volume 30 Issue 10 Pages
856-860
Published: 1977
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Acetylation of L-isoleucyl-D-alanyl-D-alanyl-L-valyl-D-leucine with acetic anhydride followed by methylation with diazomethane yielded the expected acetylpentapeptide methyl ester with molecular weight 541, but also resulted in the formation of a by-product with molecular weight 555. The incorporation of the mass corresponding to CH
2 seems to be due to ring closure-via a mixed anhydride-and methylation of the cyclol derivative thus formed. A preferred, ring-like conformation stabilized by intramolecular hydrogen bonds that in turn are the consequences of the alternation of D- and L- residues in the sequence, is invoked as explanation for the unexpected cyclization. This assumption is supported by the conversion of the pentapeptide methyl ester to desthiomalformin in molten imidazole.
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KATSUTOSHI TAKAHASHI, OSAMU YOSHIOKA, AKIRA MATSUDA, HAMAO UMEZAWA
1977 Volume 30 Issue 10 Pages
861-869
Published: 1977
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The cupric ion of the bleomycin copper complex has been shown to be reduced and transferred to a cellular protein by the following mechanism: Bleomycin-Cu
2+→Bleomycin+Cu
+ X Cu
++M→M-Cu
+ The intracellular reducing agents (
X) are suggested to be sulfhydryl compounds, because their action is inhibited by N-ethylmaleimide. The active group of the cellular protein (M) that binds with the cuprous ion is suggested to be a sulfhydryl group. The action of the bleomycin copper complex in causing DNA fragmentation in cells can be explained by the mechanism presented in this paper. This mechanism in cells is also supported by the temperature dependency of the action of the bleomycin copper complex on cells.
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G. W. GRIGG, ANNETTE M. GERO, J. MARGARET HUGHES, W. H. F. SASSE, M. B ...
1977 Volume 30 Issue 10 Pages
870-878
Published: 1977
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A wide range of aromatic compounds has been shown to amplify phleomycin-induced cell killing in
Escherichia coli. They include acridines, acridinium chlorides, dihydroanthracenes, anthracenes, dianthracenes, phenanthridinium salts, phenazinium chlorides, phenoxazones, triphenyl methane dyes, benzoquinolizinium chloride, diphenylmethane derivatives, stilbene and diphenyl derivatives. Low concentrations of these amplifiers also amplified the DNA breakage and degradation effects of phleomycin. The minimum structural specification for activity as an amplifying agent is suggested. A representative sample of compounds effective as amplifiers of phleomycin also amplified the antibiotic effects of bleomycins B4 and B6. The amplifiers described are known to vary in their ability to penetrate and accumulate in different organisms or tissues. This suggests the possibility of developing a series of antibiotic regimes using these amplifiers (or the large number of derivative compounds also likely to be active) where the therapeutic index is determined by the properties of the amplifier chosen rather than of the phleomycin or the bleomycin.
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H. HEDING, A. K. GURTU
1977 Volume 30 Issue 10 Pages
879-880
Published: 1977
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VIRENDRA KUMAR, WILLIAM A. REMERS, ROBERT GRULICH
1977 Volume 30 Issue 10 Pages
881-882
Published: 1977
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J. P. DURKIN, G. I. DMITRIENKO, T. VISWANATHA
1977 Volume 30 Issue 10 Pages
883-885
Published: 1977
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WILLIAM E. BROWN, JOSEPH SZANTO, EDWARD MEYERS, TAKESHI KAWAMURA, KEI ...
1977 Volume 30 Issue 10 Pages
886-889
Published: 1977
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HIDEO MATSUSHIMA, YASUKI MORI, KOZO KITAURA
1977 Volume 30 Issue 10 Pages
890-892
Published: 1977
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STEPHEN HANESSIAN, ROBERT MASSÉ, MARIE-LOUISE CAPMEAU
1977 Volume 30 Issue 10 Pages
893-896
Published: 1977
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VEDPAL S. MALIK
1977 Volume 30 Issue 10 Pages
897-899
Published: 1977
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TOMONOBU KUSANO, KAZUO IZAKI, HAJIME TAKAHASHI
1977 Volume 30 Issue 10 Pages
900-902
Published: 1977
Released on J-STAGE: April 12, 2006
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