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Biomedical subjects

Y Fukagawa

Publications and source records attributed to Y Fukagawa.

At least 73 records · Page 4Linked to original sources
PubMed1980

Inhibition of beta-lactamase of Bacillus licheniformis 749/C by compound PS-5, a new beta-lactam antibiotic.

By use of a new computer-assisted u.v.-spectrophotometric assay method, the kinetic parameters of the reaction catalysed by Bacillus licheniformis 749/C beta-lactamase were re-examined and the mode of inhibition of the enzyme by compound PS-5, a novel beta-lactam antibiotic, was studied with benzylpenicillin as substrate. (1) The fundamental assay conditions for the determination of Km and V were examined in detail with benzylpenicillin as substrate. In 0.1 M-sodium/potassium phosphate buffer, pH 6.8, at 30 degrees C, initial substrate concentrations of benzylpenicillin above 0.7 mM were very likely to lead to substrate inhibition. The Km value of the enzyme for benzylpenicillin at initial concentrations from 1.96 to 0.07 mM was calculated to be 97-108 microM. (2) The Km values of the enzyme for 6-aminopenicillanic acid, ampicillin and cephaloridine were found to be 25, 154-161 and 144-161 microM respectively. (3) Compound PS-5 was virtually unattacked by Bacillus licheniformis 749/C beta-lactamase. (4) The activity of the enzyme was diminished by compound PS-5, to extents depending on the duration of incubation and the concentration of the inhibitor. The rate of inactivation of the enzyme by compound PS-5 followed first-order kinetics. (5) In an Appendix, a new computer-assisted u.v.-spectrophotometric enzyme assay method, in which a single reaction progress curve of time-absorbance was analysed by the integrated Michaelis-Menten equation, was devised for the accurate and precise determination of the kinetic constants of beta-lactamase. For conversion of absorbance readings into molar substrate concentrations, the initial or final absorbance reading that was independent of the reaction time was used as the basis of calculation. In calculation of Km and V three systematic methods of data combination were employed for finer analysis of the reaction progress curve. A list of the computer program named YF6TAIM is obtainable from the author on request or as Supplementary Publication SUP 50100 (12 pages) from the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., on the terms indicated in Biochem. J. (1978) 169, 5.

Ampicillin↗
PubMed1980

PS-6 and PS-7, new beta-lactam antibiotics. Isolation, physicochemical properties and structures.

Antibiotics PS-6 and PS-7 which are shown to be 5R,6R-3-(2-acetamido)ethylthio-6-isopropyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene- 2-carboxylic acid and 5R,6R-3-(E)-(2-acetamido) vinylthio-6-ethyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid respectively, are new beta-lactam compounds isolated from fermentation broths of Streptomyces cremeus subsp. auratilis A271, S. fulvoviridis A933, S. olivaceus ATCC 31126 and S. flavogriseus NRRL 8139. Fermentation, isolation, physicochemical properties and structures of antibiotics PS-6 and PS-7 are described.

Anti-Bacterial Agents↗
PubMed1980

PS-6 and PS-7, new beta-lactam antibiotics. In vitro and in vivo evaluation.

Biological properties of two new beta-lactam antibiotics, PS-6 and PS-7, containing the carbapenem nucleus were studied. The in vitro activities of PS-6 and PS-7 were tested against clinical isolates of Gram-positive and Gram-negative bacteria in comparison with those of cefazolin, ampicillin and PS-5. In general, the antibacterial spectra of PS-6 and PS-7 were similar to that of PS-5. PS-7 was slightly less active than PS-5 and ABPC against Staphylococcus aureus. Clinical isolates of Gram-negative bacteria were found to be 2- to 8-fold more resistant to PS-6 than to PS-5, while PS-7 was 2-fold more active than PS-5 against Enterobacter, Klebsiella, Proteus, Serratia and Escherichia coli. The therapeutic effect of PS-6 seemed slightly less than that of PS-5 in an experimental infection with Staph. aureus Smith in mice.

Ampicillin↗
PubMed1980

Chemical modification of deltamycins. I. 4''-O-acyl analogs of deltamycins.

Using 4''-O-deacyldeltamycin as a starting material, various 4''-O-acyl derivatives were chemically synthesized by the following scheme: 2'-O-acetylation leads to 4''-O-acylation leads to 2'-O-deacetylation. 4''-O-Deacyldeltamycin is produced during the fermentation of deltamycin producing organisms or can be prepared by the biological deacylation of the deltamycins. 4''-O-Phenylacetyl-4''-O-deacyldeltamycin (PAD) showed good activity against various bacteria and mycoplasma. Among para-substituted PAD derivatives, NPAD (p-nitrophenylacetyl-) and SPAD (p-methylsulfonylphenylacetyl-) showed increased potency as compared to PAD against certain bacteria. The PAD was evaluated by in vivo experiments for plasma levels in mice and dogs and curative activity on the infected mice with Staphylococcus aureus Smith by subcutaneous or oral administration.

Administration, Oral↗
PubMed1980

Deacetylation of PS-5, a new beta-lactam compound, I. Microbial deacetylation of PS-5.

PS-5 was deacetylated to NS-5 (deacetylated PS-5) by l-amino acid acylase from porcine kidney and D-amino acid acylase from Streptomyces olivaceus but not by l-amino acid acylase from Aspergillus sp. Using PS-5, N-chloroacetyl-l-phenylalanine and N-chloroacetyl-D-valine as substrates, acylase producers were screened among facultative methanol-assimilating bacteria. Most of the microbes tested were active and could be classified into two groups of l-acylase producers and L-& D-acylase producers. Pseudomonas sp. 1158 which deacetylated the three substrates was chosen for further study. Cells of the bacterium entrapped in polyacrylamide gel and its acylase activities immobilized on DEAE-Sephadex were found to be useful for conversion of PS-5 to NS-5.

Acyltransferases↗
PubMed1980

Deacetylation of PS-5, a new beta-lactam compound. II. Separation and purification of L- and D-amino acid acylases from Pseudomonas sp. 1158.

L-Amino acid acylase and D-amino acid acylase of Pseudomonas sp. 1158 which converted PS-5 to NS-5 (deacetylated PS-5) were separated and purified by sonication, streptomycin and ammonium sulfate fractionations, DEAE-Sephacel column chromatography and gel filtration. Molecular weight and the isoelectric point were estimated to be 75,000 and pI 5.45 for L-amino acid acylase and 100,000 and pI 4.95 for D-amino acid acylase.

Acyltransferases↗
PubMed1980

Deacetylation of PS-5, a new beta-lactam compound. III. Enzymological characterization of L-amino acid acylase and D-amino acid acylase from Pseudomonas sp. 1158.

L-Amino acid acylase and D-amino acid acylase were stable below 50 degrees C, although the D-enzyme was more thermostable than the L-enzyme at higher temperatures. At 30 degrees C they showed the highest reaction velocity in phosphate buffer of pH 7.4. Hg++ and Cu++ severely inactivated their activity. Activation by Co++ was observed on L-amino acid acylase, but not on D-amino acid acylase. p-Chloromercuribenzoate inhibited both enzymes, whereas ethylenediamine tetraacetate was very inhibitory on L-amino acid acylase only. With N-acetyl- and N-chloroacetyl-amino acids as substrates, they were relatively stereo-specific. They acted as a peptidase on dipeptides and tripeptides. Although N-acetylglycine was attacked by the two enzymes, N-acetylglucosamine and N-acetylethanolamine were insusceptible. PS-5 was converted to NS-5 (deacetyl PS-5) by L-amino acid acylase as well as by D-amino acid acylase.

Acyltransferases↗
PubMed1979

Controlled biosynthesis of neoviridogriseins, new homologues of viridogrisein. III. Production, structures and biological properties of neoviridogriseins I and III.

The high response of our isolate of Streptomyces griseoviridus was exploited to provoke the synthesis of new viridogrisein homologues by adding various amino acids to the culture medium in an attempt to replace the alanine, sarcosine, leucine and phenylsarcosine moieties of virdogrisein. Among the amino acids added, L- and DL-alpha-amino-n-butyric acid and L-methionine gave new TLC spots which we named neoviridogriseins I and III and neoviridogrisein VII, respectively. The structures of neoviridogriseins I and III were elucidated: In both compounds, the alanine moiety of viridogrisein is replaced by a L-alpha-amino-n-butyric acid residue; furthermore, in neoviridogrisein I, the allo-hydroxy-D-proline is replaced by D-proline.

Amino Acids↗
PubMed1979

Controlled biosynthesis of neoviridogriseins, new homologues of viridogrisein. IV. In vitro synergism between neoviridogrisein II and the antibiotics of the mikamycin A group.

Neoviridogrisein II is a homologue of viridogrisein in which the hydroxyproline residue is replaced by proline. Neoviridogrisein II proved to be more active than the parent antibiotic against Gram-positive bacteria and Mycoplasma species. When neoviridogrisein II or viridogrisein was combined with griseoviridin, a non-peptidyl macrocyclic lactone, synergism was observed: maximum synergistic effect was observed for a combination ratio that depended on the test bacterium used. Neoviridogrisein II also exerted synergism when combined with mikamycin A and A-2315A.

Anti-Bacterial Agents↗
PubMed1979

PS-5, a new beta-lactam antibiotic. II. Antimicrobial activity.

PS-5, a new beta-lactam antibiotic, has relatively potent antimicrobial activity against Gram-positive and Gram-negative bacteria, especially the Enterobacter groups, Serratia marcescens, the Proteus groups and Klebsiella pneumoniae. The activity of PS-5 against many beta-lactamase-producing organisms is greater than that of cefoxitin or cefazolin. PS-5 has good therapeutic activity in mice infected with Staphylococcus aureus Smith or Enterobacter cloacae 45.

Animals↗
PubMed1979

PS-5, a new beta-lactam antibiotic. III. Synergistic effects and inhibitory activity against a beta-lactamase.

PS-5 was shown to have synergistic activity in combination with other beta-lactam antibiotics and it markedly decreased the minimum inhibitory concentration values of ampicillin or cephaloridine with a beta-lactamase-producing Proteus vulgaris strain on agar plates. The synergistic activities were also shown in bactericidal activity in liquid medium. PS-5 was shown to be inhibitory against an extracted beta-lactamase of P. volgaris.

Anti-Bacterial Agents↗
PubMed1979

Controlled biosynthesis of neoviridogriseins, new homologues of viridogrisein II. Production, biological properties and structure of neoviridogrisein II.

Our isolate of Streptomyces griseoviridus, which produced three minor factors in addition to viridogrisein and griseoviridus, which produced three minor factors in addition to viridogrisein and griseoviridin, was more sensitive to the addition of L-proline than the type culture of Streptomyces griseoviridus (NRRL2427). Yield improvement of these minor factors was attempted by the so-called controlled biosynthesis with L-proline. Addition of L-proline increased the production of neoviridogrisein II in which allo-hydroxy-D-proline in viridogrisein was replaced by D-proline.

Anti-Bacterial Agents↗
PubMed1979

Deltamycins, new macrolide antibiotics. III. Chemical structures.

The structures of deltamycins A1,A2,A3 and A4 belonging to the basic macrolide family of antibiotics were determined mainly from their spectral properties. Deltamycin A4 was identified as carbomycin A having an isovaleryl group on the mycarose moiety of the molecule. Deltamycin A1,A2 and A3 possess similarities to the structure of deltamycin A4, but they have acetyl, propionyl and n-butyryl group, respectively, in the place of isovaleryl group of deltamycin A4. These structures were confirmed by chemical synthesis from deltamycin X (4''-O-deacyldeltamycin) and the corresponding acyl chlorides.

Chemical Phenomena↗