• 제목/요약/키워드: Nucleoside

검색결과 284건 처리시간 0.026초

Characterisation of multiple substrate-specific (d)ITP/(d)XTPase and modelling of deaminated purine nucleotide metabolism

  • Davies, Oluwafemi;Mendes, Pedro;Smallbone, Kieran;Malys, Naglis
    • BMB Reports
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    • 제45권4호
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    • pp.259-264
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    • 2012
  • Accumulation of modified nucleotides is defective to various cellular processes, especially those involving DNA and RNA. To be viable, organisms possess a number of (deoxy)nucleotide phosphohydrolases, which hydrolyze these nucleotides removing them from the active NTP and dNTP pools. Deamination of purine bases can result in accumulation of such nucleotides as ITP, dITP, XTP and dXTP. E. coli RdgB has been characterised as a deoxyribonucleoside triphosphate pyrophosphohydrolase that can act on these nucleotides. S. cerevisiae homologue encoded by YJR069C was purified and its (d)NTPase activity was assayed using fifteen nucleotide substrates. ITP, dITP, and XTP were identified as major substrates and kinetic parameters measured. Inhibition by ATP, dATP and GTP were established. On the basis of experimental and published data, modelling and simulation of ITP, dITP, XTP and dXTP metabolism was performed. (d)ITP/(d)XTPase is a new example of enzyme with multiple substrate-specificity demonstrating that multispecificity is not a rare phenomenon

Gemcitabine for the Treatment of Patients with Osteosarcoma

  • Wei, Mei-Yang;Zhuang, Yan-Feng;Wang, Wan-Ming
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권17호
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    • pp.7159-7162
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    • 2014
  • Background: Patients with recurrent or refractory osteosarcoma are considered to have a very poor prognosis, and new regimens are needed to improve the prognosis in this setting. 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 recurrent or refractory osteosarcoma. Methods: Clinical studies evaluating the impact of gemcitabine based regimens on response and safety for patients with osteosarcoma were identified by using a predefined search strategy. Pooled response rates (RRs) of treatment were calculated. Results: In gemcitabine based regimens, 4 clinical studies which included 66 patients with recurrent or refractory osteosarcoma were considered eligible for inclusion. Systemic analysis suggested that, in all patients, pooled RR was 12.1% (8/66) in gemcitabine based regimens. Major adverse effects were hematologic toxicity, including grade 3 or 4 anemia, leucopenia and thrombocytopenia in gemcitabine based treatment. No treatment related death occurred in gemcitabine based treatment. Conclusion: This systemic analysis suggests that gemcitabine based regimens are associated with mild activity with good tolerability in treating patients with recurrent or refractory osteosarcoma.

계작지모탕(桂芍知母湯)의 소염.진통작용 및 Alcohol성 고뇨산혈증(高尿酸血症)에 미치는 영향 (Antiinflammatory, Analgesic and Antihyperuricemic Effects of 'Gyejakjimo-Tang' in Rats)

  • 김순신;김혜경;최종원;이정규
    • 생약학회지
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    • 제26권1호
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    • pp.66-73
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    • 1995
  • 'Gyejakjimo-Tang(桂芍知母湯)', which is composed of Cinnamon bark(桂枝), Peony root(芍藥), Anemarrhena root(知母) and other seven herbs, is described as antipyretic, diuretic and analgesic prescription in traditional medical literatures including Geumgwe-Yoryak(金櫃要略). So it is being used in the treatment of gout clinically in oriental region. As the results of the pharmacological and biochemical trials of the prescription, it was found to have antiinflammatory and significant analgesic effects indicated by carrageenin edema, dye permeabilities and writhing behavior. And it potentiated the output of uric acid in blood and the increase of uric acid in urine of alcohol-toxicated rats, which mean the decrease of uric acid level only by excretion procedure. But the prescription didn't show any effects on the activities of adenine/guanine deaminase, purine nucleoside phosphorylase, xanthine oxidase or uricase, which are related with formation and metabolism of uric acid.

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ATPase 센서를 이용한 어류근육 단백질의 $K^+-, Ca^{2}+- 및 Mg^{2+}-$ ATPase 활성의 측정 (Determination of $K^+-, Ca^{2}+- and Mg^{2+}-$ATPase activities in Fish Muscle Protein by ATPase Biosensor)

  • 천병수;김희경
    • KSBB Journal
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    • 제11권5호
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    • pp.518-523
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    • 1996
  • 효소 purine nucleoside phosphoryrase(NP)하 고 xanthine oxidase(XOD) 두 효소를 하나로 고정화시켜 산소 전극으로부터 ATPase 활성 계측용 바 이오 센서를 개발했다. 개발된 ATPase센서를 이용 해서 Thunnus albacares(Yeliowfin tuna), Tetra~ t turus audax(Striped marlin), Prognichthys agoo (Japanese flyingfish) 그리고 Cyprinus carpio ( ( Carp) 등의 각 4종의 어근육 단백질중의 $K^+-, Ca^{2}+- 그리고 Mg^{2+}-$ATPase 활성을 측정하였고, 시료 1 개를 측정는데 3분의 시간을 필요로 하였다. $K^+-, Ca^{2}+-$ATPase 활성의 경우 본 연구에셔 개발한 센 셔를 이용한 측정 결과와 종래(비색측정)법으로 측 정한 결과와의 사이에서 좋은 상관치를 얻었다.

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Potential Antidotes for T-2 Toxin Poisoning

  • Chang, I.M.;Mar, W.;Kim, J.H.;Gotvandi, H.N. Kalandi;Zong, M.
    • 생약학회지
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    • 제16권3호
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    • pp.129-135
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    • 1985
  • In order to search for potential antidotes for T-2 toxin poisoning, seven Chinese herbal drug extracts and five natural constituents were tested on mice intoxicated with T-2 toxin. When extracts of Panax ginseng and Atractylodes japonica (500 mg/kg) were administered p.o. once 3 hrs before and once 1 hr after T-2 toxin treatment, a 30% complete survival rate was noted. In case of Paeonia albiflora var. typica, a 30% complete survival rate was also produced at a dose of 250 mg/kg. Other extracts, Glycyrrhiza uralensis, Scutellaria baicalensis, Rehmannia glutinosa and Plantago asiatica exhibited no significant protection from the T-2 toxin poisoning. A nucleoside, thymidine showed protective activity against T-2 toxin toxicity and it produced a 40% complete survival rate when administered i.p. once 0.5 hr after T-2 toxin treatment. Other natural constituents, aucubin, vitamin C and E, and lipoic acid did not show any significant protective activities.

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EARLY EVENTS OCCURRING DURING LIGHT SIGNAL TRANSDUCTION IN PLANTS AND FUNGI

  • Hasunuma, Kohji;Ogura, Yasunobu;Yabe, Naoto
    • Journal of Photoscience
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    • 제5권2호
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    • pp.73-81
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    • 1998
  • Light signals constitute major factors in regulating gene expression and morphogenesis in plants and fungi. Phytochrome A and B were well characterized red and far-red light receptors in plants. Red light signals increased the phosphorylation of 18 kDa protein, which was identified to be nucleoside diphosphate (NDP) kinase. The NDP kinase catalyzed autophosphorylation and had a protein kinase activity similar to MAP (mitogen activated protein) kinase. As candidates for blue light photoreceptors, cDNAs for CRY1 and CRY2 were isolated. The N-teminal regions of these proteins showed a high hornology to DNA photolyase. The 120 kDa protein first detected in Pisurn sativurn, which showed blue light induced phosphorylation was also detected in Arabidopsis thaliana. The 120 kDa protein was encoded by the nphl gene, which regulated positive phototropism of the plant. In Neurospora crassa, blue light irradiation of the membrane fraction prepared from roycelia stimulated the phosphorylation of the 15 kDa protein, which was also identifmd to be an NDP kinase. Recent progress in understanding early events in light signal transduction mainly in Pisum sativum Alaska, Arabidopsis thaliana and Neurospora crassa was summarized.

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멸치젓의 정미성(呈味性) 5'-Mononucleotides 에 관(關)한 연구(硏究) (Studies on the Flavoring 5 '-Mononucleotides of Pickle of Small Sardine)

  • 이춘영;이계호;김형수;한인자;김상순
    • 한국식품과학회지
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    • 제1권1호
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    • pp.66-73
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    • 1969
  • More thau thirty kinds of sea food pickles have been eaten in Korea. Out of these, salted small sardine pickle was analyzed of their components and investigated the enzyme characteristics concerned. Also studied was the effect of enzymes on the production of flavorous 5'-mononucleotides. The results are summarized as follows: 1) No accumulation of flavorous 5'-mononucleotides was demonstrated because RNA-depolymerase in the raw materials and the pickles tended to decompose RNA into nucleoside and phosphoric acid. 2) 5'-Inosinic acid and 5'-adenylic acid were found in large amounts in the salted small sardine pickle. 3) 5'-Inosinic acid was contained in the salted small sardine pickle in a significant concentration, and it might be considered to be inosinic acid-type.

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Increased DNA Polymerase Fidelity of the Lamivudine Resistant Variants of Human Hepatitis B Virus DNA Polymerase

  • Hong, Young-Bin;Choi, Yong-Wook;Jung, Gu-Hung
    • BMB Reports
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    • 제37권2호
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    • pp.167-176
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    • 2004
  • Although efficient antiviral lamivudine is used for HBV-infected patients, a prolonged treatment with nucleoside analogs often results in lamivudine-resistant variants. In this study, we evaluated the fidelity of the lamivudine-resistant variants. The FLAG-tagged wild-type (FPolE) and Met550 variants (FPolE/M550A, M550V, and M550I) of HBV DNA polymerases were expressed in insect cells then purified. Like many other reverse transcriptases, no $3'{\rightarrow}5'$ exonuclease activity was detected in the HBV DNA polymerase. Since there is no proofreading activity, then the use of the site-specific nucleotide misincorporation method is beneficial. From the $f_{ins}$ value analysis, it is evident that M550I and M550V exhibit higher fidelity values than the wild-type HBV DNA polymerase, while M550A exhibits similar fidelity values. It is therefore suggested that lamivudine resistance comes from the stringency to dNTP binding and the discrimination of dCTP and lamivudine in M550V and M550I.

Synthesis and Evaluation of Antitumor Activity of a Homologous Series of $1-({\omega$}-Cyanoalkyl)-and $1,3-Bis({\omega}-cyanoalkyl)uracil$ Nucleoside Analogues

  • Kim, Jack-C.;Dong, Eun-Soo;Ahn, Jun-Won;Kim, Seon-Hee
    • Archives of Pharmacal Research
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    • 제17권3호
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    • pp.135-138
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    • 1994
  • Acyclonucleoside homologues of 1-$(\omega$-cyabnoalkyl)-and 1, 3-bis $(\omega$-cyanoalkyl) uracils were synthesized by the series of alkylation reactions of uracil with the $\omega$-chloroalkyl nitrile ${(Cl-(CH}_2)_n$-CN;n=1, 2, 3, 4) in DMSO under $50-70^circ{C}$ temperature. The 1-$(\omega$-cyanoalkyl)-and 1, 3-bis$(\omega$-cyanoalkyl) uracils were separated either by the fractional crystallization or column chromatography. The antitumor activities for these synthesized compounds were determined against four cell lines (J-82 cell, P388 cell, FM-3A cell and U-937 cell lines). These compounds failed to exhibit any significant antitumor activity.

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천연 나린게닌의 항허피스바이러스작용과 아시클로버 및 비다라빈과의 병용효과 (Antiherpetic Activities of Natural Naringenin Alone and in Combinations with Acyclovir and Vidarabine)

  • 이지현;김영소;이종길;이혁구;한성순
    • 약학회지
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    • 제43권1호
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    • pp.77-84
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    • 1999
  • To search for less toxic antiherpetic agents, the inhibitory effects of natural naringenin on the plaque formation of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in Vero cells were examined by the plaque reduction assay in vitro. Naringenin inhibited plaque formations of HSV-l and HSV-2 in a dose dependent manner. It also exhibited more potent antiherpetic activity on HSV-l with selectivity index (SI) of 19.1 than on HSV-2 with SI of 5.7 The combined antiherpetic effects of naringenin with nucleoside antiherpetic agents, acyclovir and vidarabine, were examined on the multiplication of these two strains of herpesviruses in Vero cells by the combination assay. The results of combination assay were evaluated by the combination index (CI) that was calculated by the multiple drug effect analysis. The combinations of naringenin with acyclovir on HSV-l and HSV-2 showed more potent synergism with CI values of 0.28∼0.81 for 50%, 70%, 90% effective levels than those with vidarabine with CI values of 0.86-3.28.

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