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Biomedical subjects

Shinichi Kondo

Publications and source records attributed to Shinichi Kondo.

22 records · Page 2Linked to original sources

Isolation of a novel cyclic hexadepsipeptide pipalamycin from Streptomyces as an apoptosis-inducing agent.

The novel cyclic hexadepsipeptide named pipalamycin was isolated from a culture filtrate of Streptomyces sp. ML297-90F8 as an apoptosis-inducing agent. The antibiotic was found to be consisting of each one mole of alanine, N-hydroxyalanine, glycine, N-acylated 3-hydroxyleucine, and two moles of piperazic acid. Pipalamycin induced apoptosis in apoptosis-resistant human pancreatic adenocarcinoma AsPC-1 cells at 0.3 microg/ml in 24 to approximately 48 hours. It also showed antibacterial activity on Gram-positive bacteria such as Staphylococcus aureus and Micrococcus luteus. Fermentation, isolation, structural elucidation and the biological activities of pipalamycin are described.

Adenocarcinoma↗

[Usefulness of examination of the cholesterol versus triglyceride ratio for lipoprotein fractions in a patient with marked hyper-triglyceridemia].

A patient consulted the emergency room with acute pancreatitis, hypertriglyceridemia, and diabetes mellitus, and was later admitted to the hospital. Serum levels of total cholesterol(TC) and total triglyceride (TTG), and the cholesterol(Chol) versus triglyceride(TG) ratio(Chol/TG) for lipoprotein fractions were examined periodically during the course of treatment using Chol/Trig Combo, which identifies Chol and TG by differential staining. On admission, the patient's TTG, pancreatic amylase and glucose levels were 4020 mg/dl, 2012 IU/l, and 242 mg/dl, respectively. Clinofibrate administration resulted in a decrease in Chol and TG values for all fractions. However, the Chol/TG ratios were unchanged(HDL of 0.2 to 0.4, VLDL of approximately 0.13, and LDL of 0.1 to 0.2: Reference values from 103 healthy students were as follows: HDL 5.8 +/- 2.0, VLDL 0.39 +/- 0.1, and LDL 4.9 +/- 1.3[Mean +/- SD].). During clinofibrate treatment, TC and TG values gradually increased. Clinofibrate was discontinued and fenofibrate administration was initiated. This was followed by a dramatic improvement in TC, TTG and Chol/TG values for both HDL and LDL. The monitoring of lipoprotein fraction values proved useful for determining the treatment regimen for this patient with hypertriglyceridemia.

Acute Disease↗

Polyoxypeptins A and B Produced by Streptomyces: Apoptosis-Inducing Cyclic Depsipeptides Containing the Novel Amino Acid (2S,3R)-3-Hydroxy-3-methylproline.

Potent apoptosis-inducing peptides, polyoxypeptins A (1) and B (2) were isolated from the culture broth of Streptomyces sp. by solvent extraction and column chromatography. Structural elucidation of 1 by MS and NMR analyses revealed that it is a cyclic hexadepsipeptide having a novel amino acid and a previously unrecognized N-acyl side chain. The depsipeptide consisted of 3-hydroxyleucine, N-hydroxyvaline, N-hydroxyalanine, piperazic acid, 5-hydroxyhexahydropiperazine-3-carboxylic acid, and an unusual and hitherto unreported amino acid, 3-hydroxy-3-methylproline. Alanine and valine obtained from the hydrolyzate of 1 were both in the L-configuration as concluded from chiral TLC analysis. Then, the absolute structure of 1 was determined with the relative structure obtained from X-ray crystallographic analysis, and the new amino acid was isolated and confirmed to be (2S,3R)-3-hydroxy-3-methylproline (3). MS and NMR of 2 exhibited that it is a monodeoxy compound of 1. Stereochemistry of 2 was determined by degradation studies. Both 1 and 2 at a concentration of about 0.1 &mgr;g/mL induced early cell death, nuclear fragmentation, and internucleosomal DNA scission, all of which are characteristic of apoptosis, in human pancreatic carcinoma AsPC-1 cells.

Journal Article↗

Flexible Enantiodivergent Synthesis and Biological Activity of Mannostatin Analogues, New Cyclitol Glycosidase Inhibitors.

Mannostatin A (1) is a new cyclitol inhibitor of glycoprotein processing. 2-Epimannostatin A (12) and its enantiomer (13) as well as their positional isomers (14, 15) were designed for probing structure-activity relationships in this class of glycosidase inhibitors. The analogues have been synthesized from (S)-4-((tert-butyldimethylsilyl)oxy)-2-cyclopentenone by an enantiodivergent strategy in a totally stereospecific fashion. Compound 13 showed inhibition against almond beta-glucosidase and is shown to be a topographical analogue of beta-D-glucopyranoside.

Journal Article↗