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Solubilization of Pyrimethamine, Antibacterial Drug, by Low-Molecular-Weight Succinoglycan Dimers Isolated from Shinorhizobium meliloti

  • Kim, Hwan-Hee;Kim, Kyoung-Tea;Choi, Jae-Min;Tahir, Muhammad Nazir;Cho, Eun-Ae;Choi, Young-Jin;Lee, Im-Soon;Jung, Seun-Ho
    • Bulletin of the Korean Chemical Society
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    • v.33 no.8
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    • pp.2731-2736
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    • 2012
  • The use of pyrimethamine as antibacterial drug is limited by the poor solubility. To enhance its solubility, we prepared complexes of pyrimethamine with low-molecular-weight succinoglycan isolated from Sinorhizobium meliloti. Low-molecular-weight succinoglycans are monomers, dimers, and trimers of the succinoglycan repeating unit. The monomers and dimers were separated into their three species (M1, M2, and M3) and four fractions (D1 to D4) using chromatographic techniques, which were shown to be nontoxic. The solubility of pyrimethamine was markedly increased up to 42 fold by succinoglycan D3, where the level of its solubility enhancement was even 8-20 fold higher comparing with cyclodextrin or its derivatives. The complex formation of succinoglycan D3 with pyrimethamine was confirmed by $^1H$ nuclear magnetic resonance spectroscopy, Fourier-transform infrared spectroscopy, differential scanning calorimetry, scanning electron microscopy, and molecular modeling studies. Herein, we suggest that the low-molecular-weight succinoglycans may be utilized as highly effective solubilizers of pyrimethamine for pharmaceutical purposes.

Genome-Wide Identification of Haploinsufficiency in Fission Yeast

  • Baek, Seung-Tae;Han, Sang-Jo;Nam, Mi-Young;Kim, Young-Dae;Kim, Li-La;Lee, Hyun-Jee;Heo, Kyung-Sun;Lee, Hye-Mi;Lee, Min-Ho;Park, Song-Kyu;Maeng, Pil-Jae;Park, Young-Woo;Lee, Sung-Hou
    • Journal of Microbiology and Biotechnology
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    • v.18 no.6
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    • pp.1059-1063
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    • 2008
  • Abnormal phenotypes resulting from haploinsufficiency (HI) are due to the loss of one allele. Recent studies in budding yeast have shown that HI originates from insufficient protein levels or from a stoichiometric imbalance between subunits of protein complexes. In humans, however, HI often involves transcription factors. Therefore, the species differences in HI and the molecular mechanisms of species-specific HI remain under investigation. In this study, HI in fission yeast was systematically surveyed. HI in fission yeast affected genes related to signaling and to basic cellular processes, as observed in budding yeast. These results suggest that there are species differences in HI and that the HI that occurs in fission yeast is intermediate to HI in budding yeast and humans.

Induction of Fungal Secondary Metabolites by Co-Culture with Actinomycete Producing HDAC Inhibitor Trichostatins

  • Gwi Ja Hwang;Jongtae Roh;Sangkeun Son;Byeongsan Lee;Jun-Pil Jang;Jae-Seoun Hur;Young-Soo Hong;Jong Seog Ahn;Sung-Kyun Ko;Jae-Hyuk Jang
    • Journal of Microbiology and Biotechnology
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    • v.33 no.11
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    • pp.1437-1447
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    • 2023
  • A recently bioinformatic analysis of genomic sequences of fungi indicated that fungi are able to produce more secondary metabolites than expected. Despite their potency, many biosynthetic pathways are silent in the absence of specific culture conditions or chemical cues. To access cryptic metabolism, 108 fungal strains isolated from various sites were cultured with or without Streptomyces sp. 13F051 which mainly produces trichostatin analogues, followed by comparison of metabolic profiles using LC-MS. Among the 108 fungal strains, 14 produced secondary metabolites that were not recognized or were scarcely produced in mono-cultivation. Of these two fungal strains, Myrmecridium schulzeri 15F098 and Scleroconidioma sphagnicola 15S058 produced four new compounds (1-4) along with a known compound (5), demonstrating that all four compounds were produced by physical interaction with Streptomyces sp. 13F051. Bioactivity evaluation indicated that compounds 3-5 impede migration of MDA-MB-231 breast cancer cells.

Antifungal Activities of Dimeric Sesquiterpenes, Shizukaols C and F, Isolated from Chloranthus japonicus Sieb.

  • Kang, Tae Hoon;Lee, Yun Me;Lee, Won Jung;Hwang, Eui Il;Park, Ki Duk;Choi, Gyung Ja;Moon, Jae Sun;Park, Ho-Yong;Kim, Sung Uk
    • Journal of Microbiology and Biotechnology
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    • v.27 no.7
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    • pp.1272-1275
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    • 2017
  • Two dimeric sesquiterpenes were separated from Chloranthus japonicus Sieb. and identified as shizukaols C and F. They exhibited potent antifungal activities ($MICs=4-16{\mu}g/ml$) in vitro against various plant pathogenic fungi (Pythium ultimum, Phytophthora infestans, Botrytis cinerea, Colletotrichum lagenarium, Alternaria kikuchiana, and Magnaporthe grisea). Shizukaol C showed 88% and 91% protective activities in the greenhouse against Puccinia recondita (wheat leaf rust) and Phytophthora infestans (tomato late blight), respectively, at $100{\mu}g/ml$; shizukaol F exhibited 93% antifungal activity against Puccinia recondita at the same concentration. Therefore, these compounds might serve as interesting candidates for effective antifungal agents.

Pharmacophore Mapping and Virtual Screening for SIRT1 Activators

  • Sakkiah, Sugunadevi;Krishnamoorthy, Navaneethakrishnan;Gajendrarao, Poornima;Thangapandian, Sundarapandian;Lee, Yun-O;Kim, Song-Mi;Suh, Jung-Keun;Kim, Hyong-Ha;Lee, Keun-Woo
    • Bulletin of the Korean Chemical Society
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    • v.30 no.5
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    • pp.1152-1156
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    • 2009
  • Silent information regulator 2 (Sir2) or sirtuins are NAD(+)-dependent deacetylases, which hydrolyze the acetyllysine residues. In mammals, sirtuins are classified into seven different classes (SIRT1-7). SIRT1 was reported to be involved in age related disorders like obesity, metabolic syndrome, type II diabetes mellitus and Parkinson’s disease. Activation of SIRT1 is one of the promising approaches to treat these age related diseases. In this study, we have used HipHop module of CATALYST to identify a series of pharmacophore models to screen SIRT1 enhancing molecules. Three molecules from Sirtris Pharmaceuticals were selected as training set and 607 sirtuin activator molecules were used as test set. Five different hypotheses were developed and then validated using the training set and the test set. The results showed that the best pharmacophore model has four features, ring aromatic, positive ionization and two hydrogen-bond acceptors. The best hypothesis from our study, Hypo2, screened high number of active molecules from the test set. Thus, we suggest that this four feature pharmacophore model could be helpful to screen novel SIRT1 activator molecules. Hypo2-virtual screening against Maybridge database reveals seven molecules, which contains all the critical features. Moreover, two new scaffolds were identified from this study. These scaffolds may be a potent lead for the SIRT1 activation.

Vacuum ultraviolet emission characteristics of binary and ternary gas mixtures with xenon concentration and gas pressure in AC-PDPs (AC-PDP에서 Ne-Xe의 2원 혼합기체와 He-Ne-Xe의 3원 혼합기체의 Xe 혼합비와 가스 압력에 따른 VUV 발광 특성)

  • Yoo, N.L.;Jung, K.B.;Lee, J.H.;Lee, S.B.;Han, Y.K.;Jeong, S.H.;Lee, H.J.;Son, C.G.;Lim, J.E.;Oh, P.Y.;Moon, M.W.;Jeoung, J.M.;Ko, B.D.;Cho, G.S.;Uhm, H.S.;Choi, E.H.
    • Proceedings of the Korean Institute of Electrical and Electronic Material Engineers Conference
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    • 2005.05a
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    • pp.142-145
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    • 2005
  • AC-PDP에서 발광 휘도와 발광 효율의 개선은 매우 중요한 과제중의 하나이다. 높은 발광 휘도와 발광 효율을 위해선 VUV의 높은 발광 효율이 요구되어진다. 이 실험에서는 AC-PDP에서 Ne-Xe의 2원 혼합기체와 He-Ne-Xe의 3원 혼합기체의 VUV 발광 세기를 측정하였다. 기체 압력은 200 Torr, 300 Torr, 400 Torr, 500 Torr로 유지하였고, Xe 혼합비는 1%, 2%, 4%, 7%, 10%, 15%를 사용하였다. 진공자외선 발광 세기는 He-Ne-Xe의 3원 혼합기체가 Ne-Xe의 2원 혼합기체보다 발광 세기가 훨씬 높다는 것을 알 수 있었다. 그리고 Xe 함량이 증가함에 따라 공명선인 147 nm의 발광 세기는 Xe 혼합비가 약 10%까지는 증가하다가 10% 이후에는 포화되고, 반면 분자선인 173 nm은 Xe 함량과 가스 압력이 증가함에 따라 발광 세기가 증가하였다.

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Measurement of Oblique ion-induced by electric fields secondary electron emission coefficient($\gamma$) and work function ${\Phi}w$ of the MgO protective layer in plane structure AC-PDPs (면방전 구조의 AC-PDP에서 전기장에 의해 기울어진 이온빔에 의한 MgO 보호막의 이차전자방출계수 ($\gamma$)와 일함수 (${\Phi}w$) 측정)

  • Lee, H.J.;Son, C.G.;Yoo, N.L.;Han, Y.G.;Jung, S.H.;Lee, S.B.;Lim, J.E.;Lee, J.H.;Song, K.B.;Oh, P.Y.;Jung, J.M.;Ko, B.D.;Moon, M.W.;Park, W.B.;Choi, E.H.
    • Proceedings of the Korean Institute of Electrical and Electronic Material Engineers Conference
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    • 2005.05a
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    • pp.135-138
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    • 2005
  • 현재 널리 상용되어 있는PDP는 3전극 변방전형이다. 3전극 면장전형 PDP는 주방전이 유전체 아래에 서로 평행하게 위치하고 있는 ITO투명전극 사이에서 발생한다. 따라서 방전시의 전기장은 MgO 보호막 위에서 아치형태로 형성되게 된다. 플라스마 방전 시 전자에 의해 이온화된 이온 입자들은 전기장에 의해 그 방전경로가 정해지게 된다. 물론 전기장은 표면에서 수직이지만 전기장에 의해 가속되어진 이온입자들은 MgO 보호막에 기울어져서 입사하게 된다. 따라서 플라스마 방전시의 이온들의 MgO 보호막으로의 입사각은 매우 다양하다. $\gamma$-FIB (Focused ion beam) 시스템은 이온입사에 의한 물질의 이차전자방출계수 측정에 효과적인 장비이다. 본 실험은 이러한 $\gamma$-FIB 시스템을 이용하여 다양한 각도로 입사하는 이온빔에 의한 MgO 보호막의 이차전자방출계수를 측정하였다. 또한 이온화 에너지가 다른 여러 종류의 불활성 기체를 사용하여 이온의 입사하는 각도에 따른 MgO 보호막의 일함수를 측정하였다. 이온빔의 입사각은 각각 $0^{\circ}$, $10^{\circ}$, $20^{\circ}$, $30^{\circ}$로 변화시키면서 이차전자방출계수 및 일함수를 측정하였다. 이러한 실험을 통해 입사각이 클수록 이차전자방출계수는 증가하고 일수는 감소하는 것을 확인 할 수 있었다.

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Phosphoproteomic Analysis of AML14.3D10 Cell Line as a Model System of Eosinophilia

  • Ryu, Su-In;Kim, Won-Kon;Cho, Hyun-Ju;Lee, Phil-Young;Jung, Hye-Yun;Yoon, Tae-Sung;Moon, Jeong-Hee;Kang, Sung-Hyun;Poo, Ha-Ryoung;Bae, Kwang-Hee;Lee, Sang-Chul
    • BMB Reports
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    • v.40 no.5
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    • pp.765-772
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    • 2007
  • Eosinophils act as effectors in the inflammatory reactions of allergic diseases including atopic dermatitis. Atopic dermatitis patients and others with allergic disorders suffer from eosinophilia, an accumulation of eosinophils due to increased survival or decreased apoptosis of eosinophils. In this study, a differential phosphoproteome analysis of AML14.3D10 eosinophil cell line after treatment with IL-5 or dexamethasone was conducted in an effort to identify the phosphoproteins involved in the proliferation or apoptosis of eosinophils. Proteins were separated by 2-DE and alterations in phosphoproteins were then detected by Pro-Q Diamond staining. The significant quantitative changes were shown in nineteen phosphoproteins including retinoblastoma binding protein 7, MTHSP75, and lymphocyte cytosolic protein 1. In addition, seven phosphoproteins including galactokinase I, and proapolipoprotein, were appeared after treatment with IL-5 or dexamethasone. Especially, the phospho-APOE protein was down-regulated in IL-5 treated AML14.3D10, while the more heavily phosphorylated APOE form was induced after dexamethasone treatment. These phosphoproteome data for the AML14.3D10 cell line may provide clues to understand the mechanism of eosinophilia as well as allergic disorders including atopic dermatitis.