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Biomedical subjects

K Tatsuta

Publications and source records attributed to K Tatsuta.

At least 55 records · Page 3Linked to original sources
PubMed1993

Substrate specificity of 6-deoxyerythronolide B hydroxylase, a bacterial cytochrome P450 of erythromycin A biosynthesis.

The 6-deoxyerythronolide B hydroxylase (EryF) is a soluble cytochrome P450 responsible for the stereospecific C-6 hydroxylation of the erythromycin precursor, 6-deoxyerythronolide B. Using the expression of the eryF gene in Escherichia coli [Andersen, J. F., & Hutchinson, C. R. (1992) J. Bacteriol. 174, 725-735] as the enzyme source, we examined the catalytic activity of the EryF protein toward several macrolide substrates related to 6-deoxyerythronolide B. The results of these studies were compared with measurements of the apparent dissociation constants for various substrates and with information from molecular modeling studies of the substrates and the enzyme-substrate complex. Only minor changes in the structure of 6-deoxyerythronolide B resulted in substrates with catalytic rates less than 1% of those seen with the natural substrate. Although the 9S epimer of 9-deoxo-9-hydroxy-6-deoxyerythronolide B was hydroxylated at a rate approximately equal to the natural substrate, the 9R epimer was hydroxylated at a 2-fold lower rate. Examination of molecular models revealed that the position of the 9-hydroxyl oxygen in the 9S epimer resembles that of the 9-oxo oxygen in the natural substrate more closely than in the 9R epimer. 8,8a-Deoxyoleandolide, which is identical to 6-deoxyerythronolide B except for the presence of a C-13 methyl group, and its (9S)-9-deoxo-9-hydroxy derivative were C-6 hydroxylated at a 4-fold lower rate than the natural substrate, and the 9-oxo form showed a substantially larger apparent dissociation constant.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

Synthetic studies of erythromycin derivatives. Synthesis and antimicrobial activities of 3''-EPI-erythromycin A and (9S)-11-dehydroxy-9-deoxo-9-hydroxy-11- oxoerythromycin A.

Two new derivatives, 3''-epi-erythromycin A (2) and (9S)-11-dehydroxy-9-deoxo-9-hydroxy-11-oxoerythromycin A (3), have been synthesized by using glycosylation with glycal (Ferrier rearrangement), bromomethoxylation and bis(tributyltin) oxide-bromine oxidation as the key steps. Their antimicrobial activities were compared with those of erythromycin A (1).

Anti-Bacterial Agents↗
PubMed1992

Synthesis and antitumor activity of 4'-O-acylanthracyclines.

4'-O-Acyl derivatives of doxorubicin, daunorubicin, 13-deoxocarminomycin, 13-deoxo-10-hydroxycarminomycin, 13-deoxo-11-deoxycarminomycin were synthesized through the formation and mild acid hydrolysis of 2-oxazoline intermediates. The antitumor activity of these 4'-O-acyl derivatives against P388 leukemia was similar to or more effective than the parent anthracyclines.

Animals↗
PubMed1992

Effects of macrolide antibiotics on gastrointestinal motility in fasting and digestive states.

The effect of macrolide antibiotics on gastrointestinal motility was studied in unanaesthetized dogs by using strain-gauge transducers. Midecamycin acetate, leucomycin, josamycin and acetylspiramycin, which are 16-membered macrolides, did not affect the gastrointestinal motility and no symptoms of gastrointestinal disorder were observed. On the other hand, erythromycin, roxithromycin, clarithromycin and oleandomycin, which are 14-membered macrolides, caused giant contraction and disorder symptoms. Moreover, it was found that the glycosidic linkages of the lactone ring were necessary for a structure to exert strong contractile activity.

Animals↗
PubMed1990

Inhibition of tyrosine kinase and epidermal growth factor receptor internalization by lavendustin A methyl ester in cultured A431 cells.

Lavendustin A is a novel microbial secondary metabolite that strongly inhibits tyrosine kinase in vitro. But, since it was found that it did not inhibit tyrosine kinase in situ, possibly because of its poor penetration into the cells, the authors therefore synthesized a methyl ester derivative of lavendustin A. Lavendustin A methyl ester inhibited autophosphorylation and internalization of epidermal growth factor receptor in cultured A431 cells. It also inhibited phosphatidylinositol kinase in vitro and phosphatidylinositol turnover in situ.

Cells, Cultured↗