• Title/Summary/Keyword: B. Chemical Synthesis

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A prognosis discovering lethal-related genes in plants for target identification and inhibitor design (식물 치사관련 유전자를 이용하는 신규 제초제 작용점 탐색 및 조절물질 개발동향)

  • Hwang, I.T.;Lee, D.H.;Choi, J.S.;Kim, T.J.;Kim, B.T.;Park, Y.S.;Cho, K.Y.
    • The Korean Journal of Pesticide Science
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    • v.5 no.3
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    • pp.1-11
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    • 2001
  • New technologies will have a large impact on the discovery of new herbicide site of action. Genomics, combinatorial chemistry, and bioinformatics help take advantage of serendipity through tile sequencing of huge numbers of genes or the synthesis of large numbers of chemical compounds. There are approximately $10^{30}\;to\;10^{50}$ possible molecules in molecular space of which only a fraction have been synthesized. Combining this potential with having access to 50,000 plant genes in the future elevates tile probability of discovering flew herbicidal site of actions. If 0.1, 1.0 or 10% of total genes in a typical plant are valid for herbicide target, a plant with 50,000 genes would provide about 50, 500, and 5,000 targets, respectively. However, only 11 herbicide targets have been identified and commercialized. The successful design of novel herbicides depends on careful consideration of a number of factors including target enzyme selections and validations, inhibitor designs, and the metabolic fates. Biochemical information can be used to identify enzymes which produce lethal phenotypes. The identification of a lethal target site is an important step to this approach. An examination of the characteristics of known targets provides of crucial insight as to the definition of a lethal target. Recently, antisense RNA suppression of an enzyme translation has been used to determine the genes required for toxicity and offers a strategy for identifying lethal target sites. After the identification of a lethal target, detailed knowledge such as the enzyme kinetics and the protein structure may be used to design potent inhibitors. Various types of inhibitors may be designed for a given enzyme. Strategies for the selection of new enzyme targets giving the desired physiological response upon partial inhibition include identification of chemical leads, lethal mutants and the use of antisense technology. Enzyme inhibitors having agrochemical utility can be categorized into six major groups: ground-state analogues, group specific reagents, affinity labels, suicide substrates, reaction intermediate analogues, and extraneous site inhibitors. In this review, examples of each category, and their advantages and disadvantages, will be discussed. The target identification and construction of a potent inhibitor, in itself, may not lead to develop an effective herbicide. The desired in vivo activity, uptake and translocation, and metabolism of the inhibitor should be studied in detail to assess the full potential of the target. Strategies for delivery of the compound to the target enzyme and avoidance of premature detoxification may include a proherbicidal approach, especially when inhibitors are highly charged or when selective detoxification or activation can be exploited. Utilization of differences in detoxification or activation between weeds and crops may lead to enhance selectivity. Without a full appreciation of each of these facets of herbicide design, the chances for success with the target or enzyme-driven approach are reduced.

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Azathioprine Therapy in $Henoch-Sch\"{o}nlein$ Purpura Nephritis Accompanied by Nephrotic syndrome (신증후군을 동반한 HSP 신염에서 Azathioprine의 치료 효과)

  • Son Jin-Tae;Kim Ji-Hong;Kim Pyung-Kil;Chung Hyeun-Joo
    • Childhood Kidney Diseases
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    • v.2 no.1
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    • pp.41-49
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    • 1998
  • Treatment of $Henoch-Sch\"{o}nlein$ purpura nephritis(HSPN) accomanied by nephrotic syndrome is still controversal, even though both corticosteroids and immunosuppressants have been used for therapy. Azathioprine(AZA) is a chemical analog of the physiologic purines-adenine, guanine, and hyoxanthine and an antagonist to purine metabolism which may inhibit RNA and DNA synthesis and is mainly used for immunosuppressive agent. We studied the effects of AZA in HSPN accompanied by nephrotic syndrome and evaluating the clinical status and histopathologic changes by sequential biopsies following the treatment. Fifteen patients with nehprotic syndrome either initially or during the course of HSPN confirmed by renal biopsies were treated with AZA(2 mg/kg/day) and prednisolone (0.5-1 mg/kg/day qod) for 8months. Folow up renal biopsy was done after treatment in 11 patients. The clinical status of the patients on admission were C(12 cases) and B(3 cases). Improvement of clinical status were showed in 12 cases, but 3 cases were not improved and 1 case was aggrevated after AZA treatment. Complete remission of proteinuria were in 8 cases(53.3%), partial remission were in 4 cases(26.7%) and persistence of proteinuria and hematuria were in 3 cases(20.0%). The loss of hematuria were in 10 cases(66.7%). Histopathologically and immunopathologically, 4 cases were improved. This study suggests that, although control studies are needed, AZA could be used in the treatment of HSPN accompanied by nephrotic syndrome.

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Mineralogy and Mineral-chemistry of REE Minerals Occurring at Mountain Eorae, Chungju (충주 어래산 일대에서 산출하는 희토류 광물의 광물학적 및 광물화학적 특성)

  • You, Byoung-Woon;Lee, Gill Jae;Koh, Sang Mo
    • Economic and Environmental Geology
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    • v.45 no.6
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    • pp.643-659
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    • 2012
  • The Chungju Fe-REE deposit is located in the Kyemyeongsan Formation of the Ogcheon Group. The Kyemyeongsan Formation includes meta-volcanic rocks and pegmatite hosted REE deposit which show different kind of REE-containing minerals. The meta-volcanic rocks hosted REE deposits' main REE minerals are allanite, zircon, apatite, and sphene, whereas the pegmatite hosted REE deposits is mainly composed of fergusonite, and karnasurtite, zircon, thorite. The meta-volcanic rock hosted major REE mineral is allanite as the form of aggregation and contains 23.89-29.19 wt% TREO (Total Rare Earth Oxide), 4.71-9.92 wt% $La_2O_3$, 11.30-14.33 wt% $Ce_2O_3$, 0.11-0.29 wt% $Y_2O_3$, 0.15-0.94 wt% $ThO_2$, as a formula of (Ca, Y, REE, Th)$_{2.095}$(Mg, Al, Ti, Mn, $Fe^{3+})_{2.770}(SiO_4)_{2.975}(OH)$. Accompanying REE in a coupled substitution for $Ca^{2+}$ (M1 site) and $Al^{3+}-Fe^{2+}$ (M2 site) leads to a large chemical variety. Due to the allanite's high contents of Fe, it belongs to Ferrialanite. The pegmatite hosted deposit's domi-nant REE mineral is fergusonite as prismatic or subhedral grains associated with zircon, fluorite and karnasurtite. Geochemical composition of the fergusonite($YNbO_4$) suggests substitution of Y-REE and Y-Th in A-site, and Nb-Ta-Ti in B-site, furthermore the proportion of $Y_2O_3$ and $Nb_2O_5$ is oddly 1:1.5 comparing to the ideal ratio 1:1 and Nb is higher than Y, also A-site Y actively substitutes with REE. Karnasurtite in pegmatite variously ranges 9.16-22.88 wt% $Ce_2O_3$, 2.15-9.16 wt% and $La_2O_3$, 0.44-10.8 wt% $ThO_2$, as a calculated formula (Y, REE, Th, K, Na, Ca)$_{1.478}(Ti, Nb)_{1.304}$(Mg, Al, Mn, $Fe^{3+})_{0.988}$(Si, P)$_{1.431}O_7(OH)_4{\cdot}3H_2O$. Firstly the 870-860 Ma is the initial age of the supercontinent Rhodinia dispersal and subsequent A-1 type volcanism, which contains Fe, REE, and HFS(High Field Strength elements; Nb, Zr, Y etc.) elements in Fe-rich meta-volcanic rocks dominant Kyemyeongsan Formation, might mineralized allanite. Another synthesis is that regional metamorphism at late Paleozoic 300-280 Ma(Cho et al., 2002) might cause allanite mineralization. Also pegmatite REE mineralization highly related to the granite intrusion over the Chungju area in Jurassic(190 Ma; Koh et al., 2012). Otherwise above all, A-1 type volcanism at the same time of the Kyemyeongsan Formation development, regional metamorphism and pegmatite, might have caused REE mineralization. Although REE ore bodies display a close spatial association, each ore bodies display temporal distinction, different mineral assemblage and environment of ore formation.