Probiond Co.

Seoul, South Korea

Probiond Co.

Seoul, South Korea
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Bae S.K.,Catholic University of Korea | Gwak J.,Kookmin University | Song I.-S.,Inje University | Park H.-S.,Probiond Co. | Oh S.,Kookmin University
Biochemical and Biophysical Research Communications | Year: 2011

The tumor suppressor p53 plays an important role in cellular emergency mechanisms through regulating the genes involved in cell cycle arrest and apoptosis. To identify small molecules that can activate p53-responsive transcription, we performed chemical screening using genetically engineered HCT116 reporter cells. We found that TopIn (7-phenyl-6H-[1,2,5]oxadiazolo[3,4-e]indole 3-oxide) efficiently activated p53-mediated transcriptional activity and induced phosphorylation of p53 at Ser15, thereby stabilizing the p53 protein. Furthermore, TopIn upregulated the expression of p21. WAF1/CIP1, a downstream target of p53, and suppressed cellular proliferation in various colon cancer cells. Additionally, TopIn induced DNA fragmentation, caspase-3/7 activation and poly ADP ribose polymerase cleavage, typical biochemical markers of apoptosis, in p53 wild-type and mutated colon cancer cells. Finally, we found that TopIn inhibited topoisomerase I activity, but not topoisomerase II, in vitro and induced the formation of the topoisomerase I-DNA complex in HCT116 colon cancer cells. Unlike camptothecin (CPT) and its derivative SN38, TopIn did not affect the activity of the ATP-binding cassette transporter breast cancer resistance protein (BCRP) or multidrug-resistant protein-1 (MDR-1). These results suggest that TopIn may present a promising new topoisomerase I-targeting anti-tumor therapeutics. © 2011 Elsevier Inc.

Gwak J.,Kookmin University | Hwang S.G.,SK biopharmaceuticals | Hwang S.G.,Korea University | Park H.-S.,Probiond Co. | And 9 more authors.
Cell Research | Year: 2012

The Wnt/Β-catenin pathway plays important roles in the differentiation of multiple cell types, including mesenchymal stem cells. Using a cell-based chemical screening assay with a synthetic chemical library of 270 000 compounds, we identified the compound SKL2001 as a novel agonist of the Wnt/Β-catenin pathway and uncovered its molecular mechanism of action. SKL2001 upregulated Β-catenin responsive transcription by increasing the intracellular Β-catenin protein level and inhibited the phosphorylation of Β-catenin at residues Ser33/37/Thr41 and Ser45, which would mark it for proteasomal degradation, without affecting CK1 and GSK-3Β enzyme activities. Biochemical analysis revealed that SKL2001 disrupted the Axin/Β-catenin interaction, which is a critical step for CK1- and GSK-3Β-mediated phosphorylation of Β-catenin at Ser33/37/Thr41 and Ser45. The treatment of mesenchymal stem cells with SKL2001 promoted osteoblastogenesis and suppressed adipocyte differentiation, both of which were accompanied by the activation of Wnt/Β-catenin pathway. Our findings provide a new strategy to regulate mesenchymal stem cell differentiation by modulation of the Wnt/Β-catenin pathway. © 2012 IBCB, SIBS, CAS All rights reserved.

Lee K.,University of Texas Medical Branch | Kunkeaw N.,University of Texas Medical Branch | Kunkeaw N.,Khon Kaen University | Jeon S.H.,University of Texas Medical Branch | And 8 more authors.
RNA | Year: 2011

Noncoding RNAs have drawn significant attention in biology recently. Whereas the current research is highly inclined to microRNAs, research on other noncoding RNAs has lagged behind. Here, we investigated a novel noncoding RNA that has been known as precursor microRNA miR-886 (pre-miR-886). Pre-miR-886 has been proposed also as a vault RNA, a component of the vault complex implicated in cancer drug resistance. We identified pre-miR-886 as a 102-nucleotide-long, abundant cytoplasmic RNA that is neither a genuine pre-microRNA nor a vault RNA. Pre-miR-886 is physically associated with PKR (Protein Kinase RNA-activated), an interferon-inducible and double-stranded RNA dependent kinase. The suppression of pre-miR-886 activates PKR and its downstream pathways, eIF2α phosphorylation and the NF-κB pathway, leading to impaired cell proliferation. We also found that pre-miR-886 is suppressed in a wide-range of cancer cell lines and in clinical specimens. This study is the first intense characterization of pre-miR-886 as well as the initial report on its function as a PKR regulator, which suggests a critical role in tumorigenesis. Copyright © 2011 RNA Society.

Ha E.-J.,Pusan National University | Kim K.K.,Samsung | Park H.S.,Probiond Co. | Lee S.-G.,Pusan National University | And 3 more authors.
Macromolecular Research | Year: 2013

Ni2+-Complexed poly(2-acetamidoacrylic acid) (PAAA) hydrogel support was developed for the one-step immobilization and purification of recombinant histidine-tagged glutamyl aminopeptidase (His-tagged GAP). Ni 2+-PAAA hydrogel was prepared from the polymerization of 2-acetamidoacrylic acid (AAA) and 2,2-[(1,4-dioxo-1,4-butanediyl) diamino] bis(2-propenoic acid) (DBDBPA) with potassium persulfate in dimethyl sulfoxide (DMSO), followed by Ni2+complexation. His-tagged GAP was immobilized directly from the cell lysate onto the Ni2+-PAAA hydrogel support and then purified. Catalytic activity of immobilized His-tagged GAP for the hydrolysis of alanylpara-nitroanilide revealed 90% conversion after 30 min of incubation, indicating sustained catalytic activity. The hydrogel-immobilized enzyme also exhibited enhanced thermal stability of sustained 70% activity after 1 h incubation at 60 °C, while the free enzyme activity was reduced to 50% at the same condition. After four cycles of hydrogel regeneration, the immobilized enzyme lost only 20% of its initial activity. Ni2+-PAAA hydrogel provided a new and convenient immobilization/purification system for His-tag enzymes through easy and simple procedures. © 2013 The Polymer Society of Korea.

Probiond Co. | Date: 2011-01-26

There is provided a novel method for amplifying mass spectrometric signals. More particularly, a novel method for detecting signals of a target molecule includes: i) allowing a test sample, in which it is required to determine whether or not a target molecule is present, to be contact with a gold particle whose surface is modified to selectively bind to the target molecule, ii) allowing a low molecular molecule engrafted to the gold particle to generate mass spectrometric signals after the interaction, such as binding, between the gold particle and the target molecule, and iii) amplifying the mass spectrometric signals by generating a great deal of mass spectrometric signals of the low molecular molecule even in the presence of a trace of the target molecule. Also, the assay system using the method and the gold particle prepared in the method are provided. The method may be useful to specifically amplify signals of the target molecule without any pretreatment of a test sample, which makes it possible to measure the target molecule simply and precisely.

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