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31.
Takuya Kobayakawa Nami Ohashi Yuki Hirota Kohei Takahashi Yuko Yamada Tetsuo Narumi Kazuhisa Yoshimura Shuzo Matsushita Shigeyoshi Harada Hirokazu Tamamura 《Bioorganic & medicinal chemistry》2018,26(21):5664-5671
CD4 mimics such as YIR-821 and its derivatives are small molecules which inhibit the interaction between the Phe43 cavity of HIV-1 gp120 with host CD4, an interaction that is involved in the entry of HIV to cells. Known CD4 mimics generally possess three structural features, an aromatic ring, an oxalamide linker and a piperidine moiety. We have shown previously that introduction of a cyclohexyl group and a guanidine group into the piperidine moiety and a fluorine atom at the meta-position of the aromatic ring leads to a significant increase in the anti-HIV activity. In the current study, the effects of conformational flexibility were investigated by introduction of an indole-type group in the junction between the oxalamide linker and the aromatic moiety or by replacement of the oxalamide linker with a glycine linker. This led to the development of compounds with high anti-HIV activity, showing the importance of the junction region for the expression of high anti-HIV activity. The present data are expected to be useful in the future design of novel CD4 mimic molecules. 相似文献
32.
Yasuo Imanishi Masaaki Inaba Hitoshi Seki Hidenori Koyama Yoshiki Nishizawa Hirotoshi Morii Shuzo Otani 《The Journal of steroid biochemistry and molecular biology》1999,70(4-6)
1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) is known to be involved in regulating the proliferation of parathyroid cells and PTH synthesis through reactions involving its nuclear receptor. We evaluated the effects of 1,25-(OH)2D3 and its hexafluorinated analog, 26,26,26,27,27,27-hexafluoro-1,25-dihydroxyvitamin D3 (26,27-F6-1,25-(OH)2D3), on parathyroid cells. The 1,25-(OH)2D3 and 26,27-F6-1,25-(OH)2D3 each inhibited [3H]thymidine incorporation and ornithine decarboxylase (ODC) activity, which is important in cell proliferation, in primary cultured bovine parathyroid cells. The inhibitory effect of 26,27-F6-1,25-(OH)2D3 on PTH secretion from parathyroid cells was significantly more potent than that of 1,25-(OH)2D 3 between 10−11 M and 10−8 M. Study of 26,27-F6-1,25-(OH)2D3 metabolism in parathyroid cells in vitro elucidated its slower degradation than that of 1,25-(OH)2D3. After 48 h of incubation with [1β-3H]26,27-F6-1,25-(OH)2D3, two HPLC peaks, one for [1β-3H]26,27-F6-1,25-(OH)2D3, and a second larger peak for [1β-3H]26,27-F6-1,23(S),25-(OH)3D3, were detected. No metabolites were detected after the same period of incubation with 1,25-(OH)2[26,27-3H]D3. We observed that 26,27-F6-1,23(S),25-(OH)3D3 was as potent as 1,25-(OH)2D3 in inhibiting the proliferation of parathyroid cells.Data suggest that the greater biological activity of 26,27-F6-1,25-(OH)2D3 is explained by its slower metabolisms and by the retention of the biological potency of 26,27-F6-1,25-(OH)2D3 even after 23(S)-hydroxylation. 相似文献
33.
Chen Wu David O. Kennedy Yoshihisa Yano Shuzo Otani Isao Matsui‐Yuasa 《Journal of biochemical and molecular toxicology》1999,13(2):71-76
The mechanism by which taurine (2‐aminoethanesulfonic acid) protects hepatocytes injury induced by carbon tetrachloride (CCl4) is not fully understood. In a previous study, we reported that cellular polyamines play an important role in this mechanism. The relationship between cellular glutathione (GSH), protein‐SH levels, and lactate dehydrogenase (LDH), with respect to the effect of polyamine on the cytoprotective ability of taurine in CCl4‐induced toxicity in isolated rat hepatocytes, was examined. CCl4 induced a LDH release and decreased cellular thiols and polyamine levels. Treating with taurine reversed these depletions. The effect of CCl4 was also reversed by the addition of exogenous polyamines. Pretreating with α‐difluoromethylornithine, an irreversible inhibitor of ornithine decarboxylase, which is a key enzyme in polyamine biosynthesis and therefore used to deplete cellular polyamine, prevented the protective effect of taurine. Adding diethyl maleate, a cellular glutathione‐depleting agent, reduced the effect of exogenous polyamines. The role of polyamine in the cytoprotective effect of taurine in CCl4‐induced toxicity may therefore be by preventing, among others, GSH and protein‐SH depletions. © 1998 John Wiley & Sons, Inc. J Biochem Toxicol 13: 71–76, 1999 相似文献
34.
Miwako Saikusa Naganori Nao Chiharu Kawakami Shuzo Usuku Tadayoshi Sasao Takahiro Toyozawa Makoto Takeda Ichiro Okubo 《Microbiology and immunology》2017,61(11):507-512
35.
It is known that Lassa virus Z protein is sufficient for the release of virus-like particles (VLPs) and that it has two L domains, PTAP and PPPY, in its C terminus. However, little is known about the cellular factor for Lassa virus budding. We examined which cellular factors are used in Lassa virus Z budding. We demonstrated that Lassa Z protein efficiently produces VLPs and uses cellular factors, Vps4A, Vps4B, and Tsg101, in budding, suggesting that Lassa virus budding uses the multivesicular body pathway functionally. Our data may provide a clue to develop an effective antiviral strategy for Lassa virus. 相似文献
36.
Honda K Okamoto K Mochida Y Ishioka K Oka M Maesato K Ikee R Moriya H Hidaka S Ohtake T Doi K Fujita T Kobayashi S Noiri E 《American journal of physiology. Cell physiology》2011,301(6):C1423-C1430
Maggot debridement therapy (MDT) is effective for treating intractable wounds, but its precise molecular mechanism, including the association between MDT and growth factors, remains unknown. We administered MDT to nine patients (66.3 ± 11.8 yr, 5 male and 4 female) with intractable wounds of lower extremities because they did not respond to conventional therapies. Significant increases of hepatocyte growth factor (HGF) levels were observed in femoral vein blood during 48 h of MDT (P < 0.05), but no significant change was found for vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor-β1 (TGF-β1), or tumor necrosis factor-α (TNF-α). We conducted NIH-3T3 cell stimulation assay to evaluate the relation between HGF and protease activity in excretion/secretion (ES) derived from maggots. Compared with the control group, HGF was significantly higher in the 0.05 μg/ml ES group (P < 0.01). Furthermore, protease inhibitors suppressed the increase of HGF (P < 0.05). The HGF expression was increased in proportion to the ES protein concentration of 0.025 to 0.5 μg/ml. In fact, ES showed stronger capability of promoting HGF production and less cytotoxicity than chymotrypsin or bromelain. HGF is an important factor involved in cutaneous wound healing. Therefore, these results suggest that formation of healthy granulation tissue observed during MDT results from the increased HGF. Further investigation to identify molecules enhancing HGF expression by MDT will contribute greatly to drug target discovery for intractable wound healing therapy. 相似文献
37.
Tsutsumi YM Tsutsumi R Mawatari K Nakaya Y Kinoshita M Tanaka K Oshita S 《Life sciences》2011,88(15-16):725-729
AimsCompound K (C-K; 20-O-d-glucopyranosyl-20(S)-protopanaxadiol) is a novel ginsenoside metabolite formed by intestinal bacteria and does not occur naturally in ginseng. In this study, we investigated whether administration of C-K has protective effects on myocardial ischemia-reperfusion injury and its potential mechanisms.Main methodsWe used in vivo mouse models of ischemia-reperfusion injury and performed biochemical assays in excised hearts.Key findingsC-K reduced infarct size compared with the control group after ischemia-reperfusion. Immunoblot analysis showed that C-K significantly enhanced protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS) activity. Wortmannin, a phosphoinositide 3-kinase (PI3K) inhibitor, blocked cardiac protection in vivo and attenuated phosphorylation of Akt and eNOS. Additionally, the hearts of C-K pretreated mice showed inhibition of mitochondrial swelling induced by Ca2+.SignificanceThis study showed that Compound K pretreatment has protective effects on myocardial ischemia-reperfusion injury, partly by mediating the activation of PI3K pathway and phosphorylation of Akt and eNOS. 相似文献
38.
Kiuchi M Adachi K Tomatsu A Chino M Takeda S Tanaka Y Maeda Y Sato N Mitsutomi N Sugahara K Chiba K 《Bioorganic & medicinal chemistry》2005,13(2):425-432
A practical asymmetric synthesis of both enantiomers of the immunosuppressive FTY720-phosphate (2) was accomplished, and the enantiomers were pharmacologically evaluated. Several lipases showed considerable activity and enantioselectivity for O-acylation of N-acetyl FTY720 (3) or N-benzyloxycarbonyl FTY720 (7) in combination with vinyl acetate or benzyl vinyl carbonate as the acyl donors. The synthesis using the lipase-catalyzed acylation as the key step produced the enantiomerically pure (>99.5% ee) enantiomers of 2 in multigram quantities. (S)-Isomer of 2 had more potent binding affinities to S1P(1,3,4,5) and inhibitory activity on lymphocyte migration toward S1P than (R)-2, suggesting that (S)-isomer of 2 is responsible for the immunosuppressive activity after administration of 1. Severe bradycardia was observed in anesthetized rats when (S)-2 was administered intravenously, while (R)-2 had no clear effect on heart rate up to 0.3 mg/kg. 相似文献
39.
Myelin-Associated Calpain II 总被引:7,自引:7,他引:0
Katsuhiko Yanagisawa Shuzo Sato Daniel J. O'Shannessy Richard H. Quarles Koichi Suzuki † Tadashi Miyatake 《Journal of neurochemistry》1988,51(3):803-807
Anti-chicken muscle calpain (calcium-activated neutral protease) antibody (ACAb) was found to be absorbed by purified human brain myelin when titrated by enzyme-linked immunosorbent assay, suggesting the close association of the protease with myelin. To confirm this, calcium-dependent protease was extracted from myelin membrane and purified on a phenyl Sepharose CL 4B column. It was activated by calcium ion in the millimolar range, and therefore was determined to be calpain II. This enzyme fraction was electrophoresed and immunostained with ACAb, resulting in staining as a single band with apparent molecular weight of 80K. This protease degraded exogenous myelin-associated glycoprotein. From the present results, it is suggested that calpain is bound to myelin membrane and involved in the turnover of myelin proteins. 相似文献
40.
Production and Characterization of Monoclonal Antibodies Against Myelin-Associated Glycoprotein 总被引:1,自引:1,他引:0
Masatoyo Nishizawa Masami Tanaka Takashi Inuzuka Keiko Tanaka Hiroko Baba Nobuyuki Miyatani Shuzo Sato Tadashi Miyatake 《Journal of neurochemistry》1986,47(6):1893-1900
Monoclonal antibodies against myelin-associated glycoprotein were generated by fusing mouse myeloma cells with spleen lymphocytes from BALB/c mice immunized with human myelin-associated glycoprotein purified from CNS myelin. Three groups of antibodies were identified: IgG antibodies recognizing the polypeptide moiety and IgG and IgM antibodies recognizing the carbohydrate moiety of the intact molecule. Properties of these antibodies were examined with sodium dodecyl sulfate-polyacrylamide gel electrophoresis and the immunostaining technique using human CNS and peripheral nerve myelin, and ganglioside fractions isolated from human brain and peripheral nerve, and with immunohistochemical staining of human peripheral nerves. Part of human peripheral blood mononuclear cells was stained with the antibodies against the carbohydrate moiety, but not with IgG antibodies recognizing the polypeptide moiety. Natural killer activity was partially reduced after treatment of human peripheral blood lymphocytes with an IgM antibody and complement in vitro. The possibility that anti-myelin-associated glycoprotein antibodies might play a role in the pathogenesis of demyelinating diseases through modification of natural killer activity is discussed. 相似文献