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Facile Synthesis and Radioiodine Labeling of Hypericin
Kim, Sang-Wook,Park, Jeong-Hoon,Yang, Seung-Dae,Hur, Min-Goo,Kim, Yu-Seok,Chai, Jong-Seo,Kim, Young-Soon,Yu, Kook-Hyun Korean Chemical Society 2004 Bulletin of the Korean Chemical Society Vol.25 No.8
Hypericin (1,3,4,6,8,13-hexahydroxy-10,11-dimethylphenanthro[1,10,9,8-opqra]perylene-7,14-dione), an antidepressant which is also known to be a potent protein kinase C (PKC) inhibitor was synthesized as a precursor for radioiodine labeling via two step reactions. Malignant glioma cells express higher PKC activity compared to untransformed glial cell. Here we report the synthesis and radioiodine labeling of hypericin as a potential brain tumor imaging radiopharmaceutical. The reference compound, 2-iodohypericin, and its radiolabelled analogues, 2-[$^{123}I$]iodohypericin and 2-[$^{124}I$]iodohypericin have been prepared by the reaction of hypericin with NaI or [$^{123}I$]NaI or [$^{124}I$]NaI. The labeling yield was 60-65% for each analogue and the optimal reaction time was 10 min. The purification and isolation of the labelled products were achieved by a reversed-phase HPLC.
Kim, Hoyeun,Na, Sang ,Hyeon,Lee, So-Young,Jeong, Young-Min,Hwang, Hyun-Ju,Hur, Jae ,Young,Park, Sang-Hyun,Woo, Je-Chang,Kim, Sang-Gu Portland Press Ltd. 2012 The Biochemical journal Vol.443 No.1
<P>TDP1 (tyrosyl-DNA phosphodiesterase 1), a member of the PLD (phospholipase D) superfamily, catalyses the hydrolysis of a phosphodiester bond between a tyrosine residue and the 3′-phosphate of DNA. We have previously identified and characterized the <I>AtTDP</I> gene in <I>Arabidopsis thaliana</I>, an orthologue of yeast and human <I>TDP1</I> genes. Sequence alignment of TDP1 orthologues revealed that AtTDP has both a conserved C-terminal TDP domain and, uniquely, an N-terminal SMAD/FHA (forkhead-associated) domain. To help understand the function of this novel enzyme, we analysed the substrate saturation kinetics of full-length AtTDP compared with a truncated AtTDP mutant lacking the N-terminal FHA domain. The recombinant AtTDP protein hydrolysed a single-stranded DNA substrate with <I>K</I><SUB>m</SUB> and <I>k</I><SUB>cat</SUB>/<I>K</I><SUB>m</SUB> values of 703±137 nM and (1.5±0.04)×10<SUP>9</SUP>M<SUP>−1</SUP>·min<SUP>−1</SUP> respectively. The AtTDP-(Δ1–122) protein (TDP domain) showed kinetic parameters that were equivalent to those of the full-length AtTDP protein. A basic amino acid sequence (RKKVKP) within the AtTDP-(Δ123–605) protein (FHA domain) was necessary for nuclear localization of AtTDP. Analysis of active-site mutations showed that a histidine and a lysine residue in each of the HKD motifs were critical for enzyme activity. Vanadates, inhibitors of phosphoryl transfer reactions, inhibited AtTDP enzymatic activity and retarded the growth of an <I>Arabidopsis tdp</I> mutant. Finally, we showed that expression of the <I>AtTDP</I> gene could complement a yeast <I>tdp1</I>Δ<I>rad1</I>Δ mutant, rescuing the growth inhibitory effects of vanadate analogues and CPT (camptothecin). Taken together, the results of the present study demonstrate the structure-based function of AtTDP through which AtTDP can repair DNA strand breaks in plants.</P>
Clinical outcomes of medically treated acute aortic intramural hematoma
( Min Kyu Kang ),( Jong Seon Park ),( Won Jong Park ),( Ung Kim ),( Sang Hee Lee ),( Dong Gu Shin ),( Young Jo Kim ),( Yoon Kyung Cho ),( Chang Wook Nam ),( Seung Ho Hur ),( Jin Bae Lee ),( Jae Geun R 대한내과학회 2012 대한내과학회 추계학술발표논문집 Vol.2012 No.1
Quantitative Profiling of Dual Phosphorylation of Fus3 MAP Kinase in Saccharomyces cerevisiae
Hur, Jae-Young,Kang, Gum-Yong,Choi, Min-Yeon,Jung, Jin Woo,Kim, Kwang-Pyo,Park, Sang-Hyun Korean Society for Molecular Biology 2008 Molecules and cells Vol.26 No.1
Mitogen-activated protein kinase (MAPK) signaling is a crucial component of eukaryotic cells; it plays an important role in responses to extracelluar stimuli and in the regulation of various cellular activities. The signaling cascade is evolutionarily conserved in the eukaryotic kingdom from yeast to human. In response to a variety of extracellular signals, MAPK activity is known to be regulated via phosphorylation of a conserved TxY motif at the activation loop in which both threonine and tyrosine residues are phosphorylated by the upstream kinase. However, the mechanism by which both residues are phosphorylated continues to remain elusive. In the budding yeast, Saccharomyces cerevisiae, Fus3 MAPK is involved in the mating signaling pathway. In order to elucidate the functional mechanism of MAPK activation, we quantitatively profiled phosphorylation of the TxY motif in Fus3 using mass spectrometry (MS). We used synthetic heavy stable isotope-labeled phosphopeptides and nonphosphopeptides corresponding to the proteolytic TxY motif of Fus3 and accompanying data-dependent tandem MS to quantitatively monitor dynamic changes in the phosphorylation events of MAPK. Phosphospecific immunoblotting and the MS data suggested that the tyrosine residue is dynamically phosphorylated upon stimulation and that this leads to dual phosphorylation. In contrast, the magnitude of threonine phosphorylation did not change significantly. However, the absence of a threonine residue leads to hyperphosphorylation of the tyrosine residue in the unstimulated condition, suggesting that the threonine residue contributes to the control of signaling noise.
Hur, Kyu Yeon,Kim, Soo Hyun,Choi, Min-Ah,Williams, Darren R.,Lee, Yong-ho,Kang, Sang Won,Yadav, Umesh C.S.,Srivastava, Satish K.,Jung, Mankil,Cho, Jin Won,Kim, Sang Geon,Kang, Eun Seok,Lee, Eun Jig,Le Elsevier 2010 Atherosclerosis Vol.211 No.1
<P><B>Abstract</B></P><P>Hyperglycemia-induced oxidative stress is known to play an important role in the development of several diabetic complications, including atherosclerosis. Although a number of antioxidants are available, none have been found to be suitable for regulating the oxidative stress response and enhancing antioxidative defense mechanisms. In this study, we evaluated the effects of magnesium lithospermate B (LAB) against oxidative stress. We also endeavored to identify the target molecule of LAB in vascular smooth muscle cells (VSMCs) and the underlying biochemical pathways related to diabetic atherosclerosis. Modified MTT and transwell assays showed that the increased proliferation and migration of rat aortic VSMCs in culture with high glucose was significantly inhibited by LAB. LAB also attenuated neointimal hyperplasia after balloon catheter injury in diabetic rat carotid arteries. To determine molecular targets of LAB, we studied the effects of LAB on aldose reductase (AR) activity, O-GlcNAcylation, and protein kinase C (PKC) activity in VSMCs under normoglycemic or hyperglycemic conditions and showed the improvement of major biochemical pathways by LAB. Potential involvement of the nuclear factor erythroid 2-related factor-2 (Nrf2) – antioxidant responsive element (ARE)-NAD(P)H: quinone oxidoreductase-1 (NQO1) pathway was assessed using siRNA methods. We found that LAB activates the NQO1 via the Nrf2-ARE pathway, which plays an important role in inhibition of the major molecular mechanisms that lead to vascular damage and the proliferation and migration of VSMCs. Together, these findings demonstrate that the induction of the Nrf2-ARE-NQO1 pathway by LAB could be a new therapeutic strategy to prevent diabetic atherosclerosis.</P>
Sang Won Min,Seog Ju Kim,Don Hur 대한전기학회 2013 Journal of Electrical Engineering & Technology Vol.8 No.2
In this paper, a novel approach for optimized installation and operations of battery energy storage system (BESS) and electric double layer capacitor (EDLC) modules for the renewable energy based intermittent generation is presented for them to be connected with an electric power grid. In order to make use of not merely the high energy density of battery but also the high power density of EDLC modules, it is very useful to devise the hybrid system which combines BESS and EDLC modules. The proposed method adopts the linear programming to calculate the optimized capacity as well as the quadratic programming to transmit the optimal operational signals to BESS and EDLC modules. The efficiency of this methodology will be demonstrated in the experimental study with the real data of wind speed in Texas.
Sung-Ha Lee,Min-Jung Kim,Hee-Jung Lee,Sa-Jin Kim,Jong-Sup Park,Soo-Young Hur 대한부인종양학회 2008 Journal of Gynecologic Oncology Vol.19 No.2
Metastatic Cancer of Unknown Primary Site (CUP) accounts for approximately 3-5% of all malignant neoplasms. CUP represents a heterogeneous group of metastatic tumors for which no primary site can be detected following a thorough medical history, careful clinical examination and extensive diagnostic work-up. Several authors had reported the poor prognosis of this malignancy, because there is no consensus on diagnostic guideline and optimal therapy. Historically chemotherapy has been the cornerstone of treatment for patients with CUP. We experienced a case of unknown origin inguinal lymph node squamous cell carcinoma, accompanied with carcinoma in situ of cervix. We report this case with a brief review of the literatures.