Search PubMed⌕ Search

Biomedical subjects

T Takeuchi

Publications and source records attributed to T Takeuchi.

At least 649 records · Page 36Linked to original sources
PubMed1996

Effects of ebelactone B, a lipase inhibitor, on intestinal fat absorption in the rat.

Ebelactones A and B, natural products from Streptomyces aburaviensis are potent inhibitors of pancreatic lipase. Lipase is the key enzyme required for the absorption of dietary triglycerides (TG). Ebelactone B inhibited, in a dose-dependent manner, the intestinal absorption of fat after fat-feeding in the rat. The most effective inhibition was observed when the inhibitor was administered at 60 min prior to fat-feeding. When ebelactone B (10 mg/kg) was administered, the serum levels of TG (58%) and cholesterol (36%) were decreased. Since ebelactone B effectively inhibitors absorption of dietary fat, if may provide a promising means for prophylaxis or therapeutics of hyperlipidemia and obesity.

Animals↗
PubMed1996

Piperastatin A, a new selective serine carboxypeptidase inhibitor produced by actinomycete. I. Taxonomy, production, isolation and biological activities.

Piperastatin A (structure, N-formyl-allo Ile-Thr-Leu-Val-Pip-Leu-Pip, Pip = hexahydropyridadine-3-carboxylic acid; molecular weight, 809), a new inhibitor of serine carboxypeptidase was discovered in the fermentation broth of Streptomyces lavendofoliae MJ908-WF13. It was purified by activated charcoal chromatography, YMC gel ODS-A chromatography and centrifugal partition chromatography (CPC) by monitoring its inhibitory activity against carboxypeptidase Y (CP-Y), and finally obtained as colourless needles. Piperastatin A is a competitive inhibitor of the enzyme with Ki = 52 +/- 6.2 nM. Piperastatin A is a highly specific inhibitor of the serine carboxypeptidases, CP-Y and platelet deamidase with little effect on related enzymes, has no antimicrobial activity and has low toxicity.

Carboxypeptidases↗
PubMed1996

Piperastatin A, a new selective serine carboxypeptidase inhibitor produced by actinomycete. II. Physico-chemical properties and structure determination.

Piperastatin A, a new inhibitor of serine carboxypeptidase, was discovered in the culture broth of Streptomyces lavendofoliae MJ908-WF13. The molecular formula of piperastatin A was established as C38H67N9C10 by HRFAB-MS and elemental analysis. The structure was determined to be N-formyl-allo Ile-Thr-Leu-Val-Pip-Leu-Pip (Pip = hexahydropyridadine-3-carboxylic acid) by various spectral analyses of piperastatin A and piperastatin A methylester.

Amino Acids↗
PubMed1996

Piperastatin B: a new selective serine carboxypeptidase inhibitor from Streptomyces lavendofoliae MJ908-WF13.

Piperastatin B, a new inhibitor of serine carboxypeptidase was purified from a culture broth of Streptomyces lavendofoliae MJ908-WF13 as a minor component by monitoring its inhibitory activity against carboxypeptidase Y (CP-Y). Its structure was determined to be N-formyl-Val-Thr-Leu-Val-Pip-Leu-Pip (pip: piperazic acid, hexahydropyridadine-3-carboxylic acid). Piperastatin B is a highly specific competitive inhibitor of CP-Y (Ki = 55 nM) with little effect on related enzymes and resembles the major component, piperastatin A, in these respects.

Amino Acids↗
PubMed1996

Poststatin, a new inhibitor of prolyl endopeptidase. VIII. Endopeptidase inhibitory activity of non-peptidyl poststatin analogues.

Non-peptidyl postatin analogues, (S)-N-substituted-2-[2-(1-acylpyrrolidinyl)]-2-oxoacetamides were synthesized and examined for their inhibitory activity against prolyl endopeptidase and cathepsin B in vitro. Many compounds showed stronger activity than natural poststatin, a pentapeptide. Among them, (S)-N-cyclohexyl-2-oxo-2-[2-(1-(3-phenoxybenzoyl)pyrrolidinyl)]ace tamide (22) and (S)-N-cyclohexyl-2-[2-(1-(2-naphthoyl)pyrrolidinyl)]-2-oxoacetamide++ + (19) indicated IC50 value of 5.8 and 8.2 ng/ml for prolyl endopeptidase inhibition respectively. None of these compounds possess significant inhibitory activities against cathepsin B, a cysteine protease. These results indicate that these compounds are more selective inhibitors against prolyl endopeptidase than is natural poststatin.

Magnetic Resonance Spectroscopy↗
PubMed1996

Stereospecific synthesis of a novel farnesyl protein transferase inhibitor, valinoctin A and its analogues.

(2S,3R)-3-Amino-2-hydroxyoctanoic acid was synthesized by Curtius rearrangement of an azide derivative of (S)-malic acid. Total syntheses of valinoctin A and its analogues were achieved by a coupling of (2S, 3R)-3-amino-2-hydroxyoctanoic acid moiety with L-valine or several other amino acids moieties. 2S configuration of 3-amino-2-hydroxyoctanoic acid moiety was found to be important for the inhibitory activity and the L-valine moiety of valinoctin A was exchangeable with other L-amino acids.

Alkyl and Aryl Transferases↗
PubMed1996

Antifungal antibiotic benanomicin A increases susceptibility of Candida albicans to phagocytosis by murine macrophages.

Benanomicin A is an antifungal antibiotic produced by Actinomadura spadix. In the present study, we investigated the effect of benanomicin A on the phagocytosis of Candida albicans by murine peritoneal macrophages and on the cell-surface hydrophobicity (CSH) of C. albicans. Although pretreatment of macrophages with benanomicin A had no effect on the phagocytosis, addition of benanomicin A to the culture of macrophages and Candida cells increased the susceptibility of Candida cells to the phagocytosis by the macrophages. Pretreatment of Candida cells with benanomicin A also increased the susceptibility of Candida cells to the phagocytosis. When Candida cells were mixed with benanomicin A, the antibiotic bound irreversibly to Candida cells. These data suggest the possibility that the increased susceptibility of Candida cells to the phagocytosis is mediated by the binding of benanomicin A to Candida cells. Examination of physicochemical property of Candida cell surface showed that the CSH of Candida cells significantly decreased by the treatment with benanomicin A. Thus, binding of benanomicin A to Candida cells may induce biochemical/physicochemical alternation of the surfaces, so that they become more susceptible to phagocytosis by murine macrophages. These properties of benanomicin A, along with its antifungal activity, seem to be beneficial in the treatment of fungal infections.

Animals↗
PubMed1996

Poststatin, a new inhibitor of prolyl endopeptidase. III. Optical resolution of 3-amino-2-hydroxyvaleric acid and absolute configuration of poststatin.

3-Amino-2-hydroxyvaleric acid was prepared, and separated into its diastereomers. The relative stereochemistry was determined by 1H NMR in their oxazolidone derivatives. The threo-isomer was resolved by (S)-1-(1-naphthyl) ethylamine in the N-(p-methoxybenzyloxycarbonyl) derivative. The absolute configuration of (--)-threo-3-(p-methoxybenzyloxycarbonyl)amino-2-hydroxyvaleric acid was confirmed to be 2R, 3S. The absolute configuration of 3-amino-2- oxovaleric acid in poststatin was confirmed to be S by comparison of the four stereoisomers of methyl N, O-bis(3,5-dinitrobenzoyl)-3-amino-2-hydroxyvalerate derived from 3-amino-2-hydroxyvaleric acid and that derived from 3-amino-2-oxovaleryl moiety of poststatin by means of HPLC with chiral column.

Amino Acid Sequence↗
PubMed1996

Poststatin, a new inhibitor of prolyl endopeptidase. IV. The chemical synthesis of poststain.

Total synthesis of poststatin was achieved by both liquid phase and solid phase methods. In both methods, the (2R,3S)-3-amino-2-hydroxyvaleric acid moiety was incorporated into protected pentapeptides, and was oxidized to (S)-3-amino-2-oxovaleric acid (postine). Deprotection of the oxidized pentapeptides gave a specimen identical with natural poststatin in physico-chemical properties and prolyl endopeptidase inhibitory activity.

Amino Acid Sequence↗
PubMed1996

Binding of benanomicin A to fungal cells in reference to its fungicidal action.

An antifungal antibiotic, benanomicin A, binds in the presence of Ca2+ to susceptible fungi and some bacteria, but not to antibiotic-resistant bacteria and mammalian cells. With the susceptible yeast Saccharomyces cerevisiae, benanomicin A binds similarly to whole cells and to protoplasts. Studies using benanomicin A and three structurally related derivatives suggested that a carboxylic acid in the D-alanine moiety and a sugar moiety in the benanomicin A molecule are essential for both binding and antifungal activities against growing S. cerevisiae. An amino substituent on the sugar moiety can be replaced with a hydroxyl group without the loss of activities. Benanomicin A binds to various yeast mannans which differ in glycosidic linkages. These results indicate that binding of benanomicin A to the mannan portion of fungal cells is essential for exertion of the antifungal activity.

Anthracyclines↗
PubMed1996

Hydroxymycotrienins A and B, new ansamycin group antibiotics.

New ansamycins designated hydroxymycotrienins A and B were isolated from culture broths of Bacillus sp. BMJ958-62F4. The two antibiotics inhibited more strongly the growth of human cervical cancer cell lines of human papilloma virus (HPV) positive than that of HPV negative cell lines. The structures, some biological and biochemical properties are reported.

Anti-Bacterial Agents↗
PubMed1996

Pyralomicins, novel antibiotics from Microtetraspora spiralis. III. Biosynthesis of pyralomicin 1a.

The biosynthesis of pyralomicin 1a (1) was studied by feeding of 13C and 15N labeled compounds to the culture of Microtetraspora spiralis MI178-34F18. The result indicated that the benzopyranopyrrole unit of 1 was derived from two units of acetate, one unit of propionate and one unit of proline, and that the cyclitol unit of 1 was derived from glucose metabolites. And 4'-O-CH3 was derived from the S-CH3 group of methionine.

Acetates↗
PubMed1996

New betaclamycin and aclarubicin analogs obtained by prolonged microbial conversion with an aclarubicin-negative mutant.

Microbial conversion of beta-rhodomycinone and aklavinone using an aclarubicin-negative Streptomyces galilaeus mutant afforded new anthracycline antibiotics CG21-C and CG1-C which had a rednosyl-2-deoxyfucosyl-rhodosaminyl trisaccharide residue at C-7 of each added aglycone. They were produced only when a prolonged conversion culture took place. Because the usual conversion products containing a cinerulosyl-2-deoxyfucosyl-rhodosaminyl residue were at first accumulated and then decreased during further cultivation, it was evident that they occurred by the modification of terminal cinerulose. The isolation, purification, and structural determination are described, and cytotoxicity in vitro against cultured L1210 cells and the formation mechanism are discussed.

Aclarubicin↗