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H Korenaga

Publications and source records attributed to H Korenaga.

8 recordsLinked to original sources

Structural study on a sulfated polysaccharide-peptidoglycan complex produced by Arthrobacter sp.

The structure of a sulfated polysaccharide-peptidoglycan complex (SP-PG) produced by Arthrobacter sp. was analyzed by NMR spectroscopy. In addition, oligosaccharide fragments of the SP-PG-L obtained by HF degradation were analyzed by NMR spectroscopy. These findings indicated that the sulfated polysaccharide (SP) contains a repeating unit composed of two galactofuranosides and a glucopyranoside. The main chain of the trisaccharide is [-->6) beta-D-Galf(1-->6)-beta-D-Galf(1-->ln, with beta-D-Glcp linked to one of the Galfs through a (1-->2) linkage. The sulfated positions of the trisaccharide were identified as C-3 and C-5 of the beta-glucosylated Galf residues, and C-2 or C-3 of the other Galf residue.

Arthrobacter↗

Structural studies on a sulfated polysaccharide from an Arthrobacter sp. by NMR spectroscopy and methylation analysis.

Structural characterization of a sulfated polysaccharide peptidoglycan complex (SP-PG) from an Arthrobacter sp. was performed by NMR spectroscopy and methylation analysis. In order to simplify the analyses, the desulfated SP-PG was used. NMR spectroscopy revealed the presence of a trisaccharide repeating unit and a disaccharide repeating unit. The trisaccharide unit was composed of two galactofuranosides and one glucopyranoside, and the disaccharide unit was of two galactopyranosides, as shown below. The methylation analysis showed that the polysaccharide consists mainly of a 4-linked galactopyranoside, a 6-linked galactopyranoside, a 6-linked galactofuranoside, a 2,6-linked galactofuranoside, a terminal galactopyranoside and a terminal glucopyranoside. These findings confirmed the structure indicated by the NMR spectroscopy. The repeating units determined in this study are novel.

Arthrobacter↗

Anti-angiogenesis agent DS-4152 is a potent and selective inhibitor of HIV-1 replication in vitro.

OBJECTIVE: To determine whether the anti-angiogenesis agent DS-4152 inhibits the replication of HIV-1 in vitro. DESIGN: A sulfated polysaccharide-peptidoglycan DS-4152 has recently been identified as a potent and selective inhibitor of Kaposi's sarcoma (KS). Therefore, it is important to evaluate the anti-HIV-1 activity of DS-4152 alone and in combination with dideoxynucleosides. METHODS: Activity of DS-4152 against HIV-1 replication was examined in MT-4, Molt-4, and peripheral blood lymphocyte cells. The inhibitory effect of the compound on syncytium-formation was determined by cocultivation of Molt-4 cells with Molt-4/IIIB cells. Inhibition of virus adsorption to the host cells was measured by a p24 antigen capture enzyme-linked immunosorbent assay. RESULTS: DS-4152 showed potent and selective inhibition of HIV-1 replication in the cell systems. Its 50% effective concentration for HIV-1 (IIIB strain) in MT-4 cells was 0.7 microgram/ml. The compound was not cytotoxic at concentrations < or = 100 micrograms/ml. DS-4125 proved inhibitory to syncytium-formation and virus adsorption. The anti-HIV-1 activities of zidovudine, dideoxycytidine and dideoxyinosine were not affected by the presence of DS-4152. CONCLUSION: DS-4152 has the potential, from these in vitro studies, to function as an anti-HIV-1 as well as an anti-angiogenesis agent. In order to determine this possibility, consequences of DS-4152 infusion on HIV-1 p24 serum levels and CD4+ cell counts over time are being examined in ongoing clinical trials in the United States on patients with AIDS-associated KS.

Antiviral Agents↗

Antitumor effects of an antiangiogenic polysaccharide from an Arthrobacter species with or without a steroid.

A sulfated polysaccharide-peptidoglycan complex, DS-4152, isolated from the culture supernatant of an Arthrobacter species inhibited angiogenesis and tumor growth and enhanced the antiangiogenic activity of 11 steroid hormones by 2 to 100 times. In the presence of cortisone acetate or tetrahydro S, DS-4152 suppressed chick chorioallantoic membrane angiogenesis and murine tumor M5076 cell-induced s.c. angiogenesis. The antitumor effects of DS-4152 administered in combination with a steroid whose dose level did not affect tumor growth were examined. DS-4152 significantly inhibited the growth of s.c.-implanted B16 melanoma in combination with cortisone acetate. DS-4152 plus tetrahydro S inhibited the growth of s.c. solid tumors and prolonged the survival time of mice bearing highly metastasizing M5076. The body weight increase was not affected by any administration. On the other hand, the survival of mice with ascitic M5076 tumors was not affected by the combination of DS-4152 plus tetrahydro S. The antiangiogenic activity of DS-4152 was more potent than that of heparin. Furthermore, DS-4152 is an angiogenesis inhibitor by itself, without steroid hormones. Successive s.c. treatment with heparin caused hemorrhagic death, but with DS-4152, suppressed tumor growth without reducing body weight.

Animals↗

The sulfated polysaccharide-peptidoglycan complex potently inhibits embryonic angiogenesis and tumor growth in the presence of cortisone acetate.

In combination with cortisone acteate, the sulfated polysaccharide (SP)-peptidoglycan (PG) complex produced by an Arthrobacter species was found to inhibit both embryonic angiogenesis of chick chorioallantoic membrane (CAM) and growth of solid Sarcoma 180 tumor in mice. Three fractions obtained from the SP-PG complex by gel filtration showed a great difference in the inhibitory effect on angiogenesis of the CAM, whereas in ex vivo study such a difference was reduced. Of the three fractions, SP-PG-L having the lowest molecular weight and peptidoglycan content exhibited the highest antiangiogenic and antitumor activities, even higher than those of heparin. Neither desulfation nor sulfation of the SP-PG complex greatly affected the antiangiogenic activity, and dextran sulfates and mannoglucan sulfates were lacking the activity. This suggested that glycosyl sequences of sulfated polysaccharides are more important for the activity, rather than content or intramolecular distribution of sulfate groups.

Allantois↗

Antithrombotic and thrombolytic effects of galactan polysulfate (DH 6322) in rats.

Anticoagulant, fibrinolytic and thrombolytic effects of galactan polysulfate (DH 6322), a new semi-synthetic polysaccharide sulfate of bacterial origin, were studied in the rat in vitro, ex vivo and in vivo. Addition of DH 6322 to citrated plasma gave a 50% reduction in euglobulin lysis time at around 50 micrograms/ml and a 2-fold prolongation in plasma recalcification time at 40 micrograms/ml. Intravenous injection of DH 6322 caused significant acceleration of euglobulin clot lysis and urokinase-induced plasma clot lysis at doses as low as 2 mg/kg, and also significant prolongation of plasma recalcification time. Oral application of the compound gave similar effects only at an extremely high dose of 3 g/kg. When injected intravenously before induction of pulmonary thrombosis by lactic acid infusion, DH 6322 was found to be effective in preventing thrombus formation. In progressive venous thrombosis induced by insertion of a steel coil into the inferior vena cava, DH 6322 treatment also caused a significant reduction of thrombus size together with increase in the serum levels of fibrin degradation products. The findings indicate that the antithrombotic effects of DH 6322 result from its enhancement of the fibrinolytic potential as well as its anticoagulative action.

Animals↗

A sulfated polysaccharide produced by an Arthrobacter species.

A new sulfated polysaccharide was isolated from the culture supernatant of a strain of Arthrobacter sp. The polysaccharide purified with quaternary ammonium salts consists of D-galactose, D-glucose, sulfate, phosphorus, glucosamine, muramic acid, alanine, glutamic acid, glycine, and LL-diaminopimelic acid in a molar ratio of 56 : 9.0 : 68 : 6.4 : 2.0 : 1.1 : 2.1 : 1.0 : 1.2 : 1.2. The presence of the two amino sugars and four amino acids suggests that the polysaccharide, which is principally a galactan sulfate, contains small amounts of so-called peptidoglycan and that it is derived from the bacterial cell-wall polysaccharide. Gel filtration indicates the heterogeneity of the purified polysaccharide in its peptidoglycan content and molecular size. The molecular weight of its major portion was estimated to be 2.3 X 10(4) by gel filtration. The fractions GS-I and GS-II, and GS-4M and GS-5M, which were obtained by fractionation of the polysaccharide on Sephacryl S-200 and Dowex 1-X2 (Cl- form), respectively, gave almost the same chemical composition as the original polysaccharide, except in the peptidoglycan content, indicating that this polysaccharide is a series of complexes composed of essentially equal, sulfated polysaccharide chains and peptidoglycan fragments in their various ratios. The polysaccharide has [alpha]D -36 degrees and is composed predominantly of beta-glycosidic linkages, as judged from its specific optical rotation (-37 degrees) and the infrared absorption (885 cm-1) of its desulfated material. It exhibits a potent antithrombin activity (ID50, 0.82 micrograms/ml). A possible partial structure of the polysaccharide is also discussed, based on the results of periodate oxidation, Smith degradation, and alkali treatment.

Arthrobacter↗