• Title/Summary/Keyword: Nucleoside

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A Nudix Hydrolase Protein, Ysa1, Regulates Oxidative Stress Response and Antifungal Drug Susceptibility in Cryptococcus neoformans

  • Lee, Kyung-Tae;Kwon, Hyojeong;Lee, Dohyun;Bahn, Yong-Sun
    • Mycobiology
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    • v.42 no.1
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    • pp.52-58
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    • 2014
  • A nucleoside diphosphate-linked moiety X (Nudix) hydrolase-like gene, YSA1, has been identified as one of the gromwell plant extract-responsive genes in Cryptococcus neoformans. Ysa1 is known to control intracellular concentrations of ADP-ribose or O-acetyl-ADP-ribose, and has diverse biological functions, including the response to oxidative stress in the ascomycete yeast, Saccharomyces cerevisiae. In this study, we characterized the role of YSA1 in the stress response and adaptation of the basidiomycete yeast, C. neoformans. We constructed three independent deletion mutants for YSA1, and analyzed their mutant phenotypes. We found that ysa1 mutants did not show increased sensitivity to reactive oxygen species-producing oxidative damage agents, such as hydrogen peroxide and menadione, but exhibited increased sensitivity to diamide, which is a thiol-specific oxidant. Ysa1 was dispensable for the response to most environmental stresses, such as genotoxic, osmotic, and endoplasmic reticulum stress. In conclusion, modulation of YSA1 may regulate the cellular response and adaptation of C. neoformans to certain oxidative stresses and contribute to the evolution of antifungal drug resistance.

Novel Synthesis of Sulfated Chitosan Derivatives and its Anti-HIV-1 Activity (황산화 키토산 유도체의 합성과 항에이즈활성)

  • Han Sang-Mun
    • Journal of environmental and Sanitary engineering
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    • v.21 no.1 s.59
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    • pp.21-34
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    • 2006
  • To investigate anti-HIV-1 activity of water soluble chitosans, sulfated chitosan derivatives were prepared in mild condition. Various sulfated chitosan derivatives (N-3,6-O-S-chitosan, N-desulfated 3,6-O-S-chitosan, 3,6-O-S-chitin, and 3,6-O-sulfated-N-(o-carboxybenzoyl) chitosan) were synthesized with sulfurtrioxidepyridene complex in pyridine solvent. Characterization of the sulfated chitosan derivatives was carried out by $^{13}C$ NMR and IR spectroscopies. To observe ionic reaction properties, pKas of the sulfated chitosan derivatives and chitosan of low molecular weight were estimated by potentiometric titration. The sulfated chitosan derivatives had high water solubility, pKas (pKa : 7.7) of N-3,6-O-S-chitosan and N-desulfated 3,6-O-S-chitosan were increased than pKa of water insoluble chitosan (pKa : 6.2), These results suggest the participation of electrostatic interaction of amino and sulfate groups on the sulfated chitosans. Anti-HIV-1 drugs, such as AZT, ddC, and ddI for anti-HIV activity had higher selective index compared with SCB-chitosan but N-3,6-O-S-chitosan has shown higher selective index compared with ddC and ddI as HIV drugs.. These results suggest that sulfated chitosan derivatives were expected as an anti-HIV drug with differential driving force mechanism against some nucleoside analogs drug in the future.

A Nucleoside with Lipid Peroxidation Inhibitory Activity from Agrocybe cylindracea. (버들송이로부터 분리한 Nucleoside계 화합물의 지질과산화 저해활성)

  • 이인경;윤봉식;유익동
    • Microbiology and Biotechnology Letters
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    • v.26 no.6
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    • pp.558-561
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    • 1998
  • In the screening for lipid peroxidation inhibitors from edible mushroom, Agrocybe cylindracea, a bioactive compound AG 8 was isolated. The AG 8 was purified from methanol extract of its fruit body by Diaion HP-20 column chromatography, ethyl acetate extraction, and silica gel column chromatography, consecutively. Based on various NMR studies including $^1$H irradiation and HMBC experiments, the AG 8 was identified as MTA, 5'-deoxy-5'-methylthioadenosine. This compound inhibited lipid peroxidation with an $IC_{50}$/ value of 3.2 $\mu\textrm{g}$/$m\ell$. The MTA was isolated for the first time from basidiomycetes.

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Synthesis of Adenosine and Uridine Analogues Containing Conjugated Diene (공액 이중 결합을 갖는 Adenosine과 Uridine 유사체의 합성)

  • Ro, Bong Oh
    • Journal of the Korean Chemical Society
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    • v.45 no.4
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    • pp.312-317
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    • 2001
  • 7'-Aldehyde-nucleosides analogue (2a, 2c) were synthesized from 6-N-benzoyl-2',3'-O-isopropylideneadenosine and uridine. The condensation of 2 with ethoxycarbonylmethylene Wittig reagent produced the adenosine and uridine analogues containing extended conjugated diene and ethoxycarbonyl group, ethyl-1',5',6',7',8'-pentadeoxy-1'-(adenin-9-yl)-$\beta$-D-ribo-nona-5'(E),7'(E)-dienofuranuronate (4b) and ethyl-1'. 5',6',7',8'-pentadeoxy-1'-(uracil-1-yl)-$\beta$-D-ribo-nona-5'(E),7'-(E)-dienofuranuronate (4c). 9-[8',8'-dibromo-5',6',7',8' -tetradeoxy-$\beta$-D-ribo-octa-5'(E),7'(E)-diene]nucleosides (6b, 6c) were also prepared from 2 with similar method.

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Effect of Sustained-Release of Adenosine by Elvax 40P Implant on Mouse Mammary Development (생쥐의 유선발달에 있어서 Elvax 40P Implant를 이용한 서방형 Adenosine의 역할)

  • 여인서;박춘근;홍병주
    • Korean Journal of Animal Reproduction
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    • v.16 no.4
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    • pp.387-397
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    • 1993
  • To examine local response of adenosie(purine nucleoside) on the developing mammary gland, Elvax 40P implants containing adenosine were surgically implanted into mammary fat pad of the five week old female ICR mice. Inguinal(the 4th) mammary glands of anesthetized mice were exposed andplaced the implants for 12 days. One gland was treated with an adenosine implant, while the contralateral gland received a blank implant as control. For whole-mount preparations, glands were stained with alum carmine, and for histological observation, micro-selected mammary glands were stained with hematoxylin and eosin Y. Implantation with Elvax 40P did not affect on the damage of neighboring mammary tissue. Adenosie 25 or 250$\mu\textrm{g}$ per slow-release implant stimulated local mammary end bud formation of ovariectomized mice such as end bud size and numbers of end bud per gland in a dose dependent manner(P<0.05), and lower concentration of adenosie(2.5 or 25$\mu\textrm{g}$/implant) increased numbers of end bud(P<0.05) and end bud size(P<0.1) of intact mice. Adenosine treatment and intact ovarian function had moderate interation effects on the stimulation of end bud formation at 2.5$\mu\textrm{g}$ adenosine/implant(P<0.1). In histological observation, adenosine implants increased numbers of mammary epithelial type of cells at mammary duct in the presence or absece ofovary. These results indicate that adenosine should be one of regulators in mouse mammary ductal growth.

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Conjugal Transfer of Plasmid DNA from Escherichia coli to Streptomyces lavendulae RFI-5

  • KITANI, SHIGERU;BIBB, MERVYN J.;NIHIRA, TAKUYA;YAMADA, YASUHIRO
    • Journal of Microbiology and Biotechnology
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    • v.10 no.4
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    • pp.535-538
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    • 2000
  • Streptomyces lavendulae FRI-5 produces the ${\gamma}$-butyrolactone autoregulator IM-2, which is required for nucleoside antibiotic producetion. We have developed a system for introducing DNA into S. lavendule FRI-5 via conjugal transfer from Esherichia cole. Conditions were established for conjugation of the oriT-and attP-containing plasmid pSET152 from E. coli ET12567 (pUZ8002) to FRI-5. Conjugation resulted in integration of the plasmid at the chromosomal C31 attB site. The frequency of intergeneric conjugation varied with the medium used. The highest frequency ($1.6\times10-5$ per recipient) was obtained on ISP medium 2 containing 10mM MgCl2. Southern blot and phenotypic analyses of exconjugants revealed that S. lavendulae FRI-5 contains a unique C31 attB site, and that integration of heterologous DNA into the attB site did not interfere with morphological differentiation or IM-2-dependent signal transduction, including the production of a blue pigment. This system will now enable detailed genetic analysis of the regulation of antibiotic production in S. lavendulae FRI-5.

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Inhibition of Herpes Simplex Viruses, Types 1 and 2, by Ginsenoside 20(S)-Rg3

  • Wright, Stephen M.;Altman, Elliot
    • Journal of Microbiology and Biotechnology
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    • v.30 no.1
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    • pp.101-108
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    • 2020
  • Infections by herpes simplex viruses have an immense impact on humans, ranging from self-limiting, benign illness to serious, life-threatening diseases. While nucleoside analog drugs are available, resistance has been increasing and currently no vaccine exists. Ginsenosides derived from Panax ginseng have been documented to inhibit several viruses and bolster immune defenses. This study evaluated 12 of the most relevant ginsenosides from P. ginseng for toxicities and inhibition of herpes simplex viruses types 1 and 2 in Vero cells. The effects of test compounds and virus infection were determined using a PrestoBlue cell viability assay. Time course studies were also conducted to better understand at what points the virus life cycle was affected. Non-toxic concentrations of the ginsenosides were determined and ranged from 12.5 μM to greater than 100 μM. Ginsenoside 20(S)-Rg3 demonstrated the greatest inhibitory effect and was active against both HSV-1 and HSV-2 with an IC50 of approximately 35 μM. The most dramatic inhibition-over 100% compared to controls-occurred when the virus was exposed to 20(S)-Rg3 for 4 h prior to being added to cells. 20(S)-Rg3 holds promise as a potential chemotherapeutic agent against herpes simplex viruses and, when used together with valacyclovir, may prevent increased resistance to drugs.

Pathomorphological Peculiarity of Dometic Silkworm, Bombyx mori. Infected with Cordyceps, Paecilomyces tenuipes (동충하초 감염 누에의 병리형태학적 특성)

  • Yun, Jae-Su
    • The Korean Journal of Pesticide Science
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    • v.13 no.3
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    • pp.177-184
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    • 2009
  • This study was carried out to investigate infection process, symptoms and main component of the domestic silkworm, Bombyx mori. larvae and pupa infected with the entomopathogenic fungus Cordyceps, Paecillomyces tenuipes. The Cordyceps, Paecillomyces tenuipes, was highly infectious to the silkworms. A pathogenicities of Cordyceps, Paecillomyces tenuipes, may be highly virulent because of the low resistance or high susceptibility of the silkworms. The silkworm larva infected with Cordyceps formed phialospores on the phialides at the imperfect stage of the genus Cordyceps, But silkworm pupa infected with Cordyceps formed ascospores in the asci at the perfection stage of the genus Cordyceps. The results of analysis of health silkworm pupa and silkworm pupa infected with Cordyceps were obtained that amino acid, fatty acid, and nucleoside were very different.

Gemcitabine in Treating Patients with Refractory or Relapsed Multiple Myeloma

  • Zheng, Hua;Yang, Fan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.21
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    • pp.9291-9293
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    • 2014
  • Background: Patients with refractory or relapsed multiple myeloma are considered to have a very poor prognosis, and new regimens are needed to improve the outcome. Gemcitabine, a nucleoside antimetabolite, is an analog of deoxycytidine which mainly inhibits DNA synthesis through interfering with DNA chain elongation and depleting deoxynucleotide stores, resulting in gemcitabine-induced cell death. Here we performed a systemic analysis to evaluate gemcitabine based chemotherapy as salvage treatment for patients with refractory and relapsed multiple myeloma. Methods: Clinical studies evaluating the impact of gemcitabine based regimens on response and safety for patients with refractory and relapsed multiple myeloma were identified by using a predefined search strategy. Pooled response rate (RR) of treatment were calculated. Results: In gemcitabine based regimens, 3 clinical studies which including 57 patients with refractory and relapsed multiple myeloma were considered eligible for inclusion. Systemic analysis suggested that, in all patients, pooled RR was 15.7% (9/57) in gemcitabine based regimens. Major adverse effects were hematologic toxicity, including grade 3 or 4 anemia, leucopenia and thrombocytopenia i. No treatment related death occurred with gemcitabine based treatment. Conclusion: This systemic analysis suggests that gemcitabine based regimens are associated with mild activity with good tolerability in treating patients with refractory or relapsed multiple myeloma.

Synthesis of Methyl-substituted Bicyclic Carbanucleoside Analogs as Potential Antiherpetic Agents

  • Kim, Kyung-Ran;Park, Ah-Young;Lee, Hyung-Rock;Kang, Jin-Ah;Kim, Won-Hee;Chun, Pu-Soon;Bae, Jang-Ho;Jeong, Lak-Shin;Moon, Hyung-Ryong
    • Bulletin of the Korean Chemical Society
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    • v.29 no.10
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    • pp.1977-1982
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    • 2008
  • Novel bicyclo[3.1.0]hexanyl purine nucleoside analogues were synthesized as potential antiherpetic agents via a bicyclo[3.1.0]hexanol (${\pm}$)-8, which was prepared using a highly efficient carbenoid cycloaddition reaction. A highly diastereoselective reduction of ketone and a Mitsunobu reaction for the condensation of glycosyl donor (${\pm}$)-12 with 6-chloropurine were employed.