• Title/Summary/Keyword: binding agent

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Conformational Analysis of Sulfonylureas : Acetohexamide and Tolazamide (Sulfonylurea 유도체들의 구조분석 : Acetohexamide와 Tolazamide)

  • 정우태;강기롱;이성희
    • YAKHAK HOEJI
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    • v.39 no.3
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    • pp.329-336
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    • 1995
  • Conformational free energy calculations using an empirical potential function and a hydration shell model(program CONBIO) were carried out on hypoglycemic agent acetohexamide and tolazamide in the unhydrated and hydrated states. The initial geometry of sulfonylureas was obtained from X-ray crystallographieal data and homologous molecular fragments. In both states, the feasible conformations were obtained from the calculations of conformational energy, conformational entropy, and hydration free energy by varying all the torsion angles of the molecules. From the calculation results, it is known that the conformations] entropy is the major contribution to stabflize the low-free-energy conformations of two sulfonylureas in both states. But, in hydrated state, the hydration does not directly affect each conformations. The intramolecular hydrogen bonding of sulfonylurea hydrogen and 7-membered nitrogen appeared to the conformations of tolazamide in both states. It is thought that the hydrogen bonding decrease steric hindrance on the receptor binding direction. The substitution of alicyclic or N-heterocyclic ring than that of carbons chain of urea moiety may be properly interaction between sulfonylureas and the putative pancreatic receptor.

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Glial Cell-specific Regulation of the JC virus Early Promoter by Silencer and DNA Methylation (Silencer 및 DNA methylation에 의한 JC virus early promoter의 뇌교세포 특이적인 조절)

  • 김희선;우문숙
    • YAKHAK HOEJI
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    • v.46 no.2
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    • pp.143-148
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    • 2002
  • The human polyomavirus JC virus is the etiologic agent of progressive multifocal leukoencephalopathy (PML). The JC virus early promoter directs cell-specific expression of the viral replication factor large T antigen, thus transcriptional regulation constitutes a major mechanism of glial tropism in PML. Here we found that pentanucleotide sequence immediately upstream of the TATA sequence functions as a cell-specific silencer in the JC virus transcription. In vitro binding studies showed that synthetic oligonucleotides spanning a pentanucleotide sequence, designated "oligo 2", interacts with nuclear proteins from non-glial cells in a cell-specific manner. Furthermore, the sequence preferentially repressed the heterologous thymidine kinase promoter activity in non-glial cells. We also tested whether JC virus transcription is controlled by DNA methylation. Transient transfection of in vitro methylated JC virus promoter abolished transcription in both the glial and non-glial cells. The repression fold was much larger in glial cells than in non-glial cells. Taken together, this finding suggests that glial cell-specific expression of the JC virus is controlled by DNA methylation as well as cell-specific silencers.

The Facile and Efficient Synthesis of 8-Chloroadenosine $3^I,5^I$-cyclic monophosphate by phosphorylative cyclization of 8-chloroadenosine and its characterization by$^1 H and 13^C$ NMR spectroscopy

  • Woo, Nam-Tae;Jin, Sun-Yong;Cho, Dae-Jin;Kim, Nam-Sun;Bae, Eun-Hyung;Jung, Jee-Hyung;Ham, Won-Hun;Jung, Young-Hoon
    • Archives of Pharmacal Research
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    • v.20 no.2
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    • pp.176-179
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    • 1997
  • Purine nucleosides were chlorinated by the reaction of acyl chloride in DMF with MCPBA under mild conditions with moderate yields. And, satisfactory method for the synthesis of ribonucleoside-$3^{I},5^{I}$-cyclic phosphates and its characterization by$^{1}H$ and $^{13}C$ nmr spectroscopy is described.

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The Study of Doxorubicin and its Complex with DNA by SERS and UV-resonance Raman Spectroscopy

  • Lee, Chul-Jae;Kang, Jae-Soo;Kim, Mak-Soon;Lee, Kwang-Pill;Lee, Mu-Sang
    • Bulletin of the Korean Chemical Society
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    • v.25 no.8
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    • pp.1211-1216
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    • 2004
  • The interaction of the antitumour agent doxorubicin with calf thymus DNA is investigated in an aqueous solution at a pH level of 6-7 with molar ratios of 1/10. A UV-resonance Raman spectroscopy and surface enhanced Raman spectroscopy are used to determine the doxorubicin binding sites and the structural variations of doxorubicin-DNA complexes in an aqueous solution. Doxorubicin intercalates with adenine and guanine via a hydrogen bond formation between the N7 positions of purine bases and the hydroxyl group of doxorubicin.

Investigation of the Binding Affinity between Styrylquinoline Inhibitors and HIV Integrase Using Calculated Nuclear Quadrupole Coupling Constant (NQCC) Parameters (A Theoretical ab initio Study)

  • Rafiee, Marjan A.;Partoee, Tayyebe
    • Bulletin of the Korean Chemical Society
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    • v.32 no.1
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    • pp.208-212
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    • 2011
  • In this work, the calculated nuclear quadrupole coupling constants of $^{17}O$ in some styrylquinoline conformers were presented. The calculations were carried out to find the relationships between the charge distribution of styrylquinolines and their pharmaceutical behavior and to explore the differences among the electronic structures of some conformers of these potent HIV IN inhibitors. Furthermore, the HIV IN inhibitory of R1 and R2 rotamers was compared. On the basis of our results: - Charge density on oxygen atoms of carboxyl moiety has a dominant role in the drug activity. - The a conformer in which a divalent hydrogen atom is a link, has more capability in antiviral drug treatment. - The R1 conformer, as a $Mg^{+2}$ chelating agent, is better than R2 conformer and thus it is more inhibitor of HIV IN.

Quality and Yield Improvement Analysis of CNT Oil Sensor (CNT Oil Sensor의 특성과 수율 향상 분석)

  • Park, Jung-Ho;Lee, Eui-Bok;Lau, Vincent;Ju, Byeong-Kwon
    • Journal of the Korean Institute of Electrical and Electronic Material Engineers
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    • v.24 no.8
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    • pp.682-685
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    • 2011
  • An engine oil sensor based on multiwall carbon nanotubes was fabricated with screen printing method. Since carbon nanotubes are generally intertwined, dispersion of the carbon nanotubes in the binding agent (ethyl cellulose, a-terpineol, frit) is a key factor for large yield of engine oil sensor. By conventional dispersion method, a hand-mill method, the maximum yield was 80% at most. However, we used the hand ultrasonic, in order to increase the yield of the sensors. As a results, our engine oil sensor fabricated by the screen printing method shows excellent yield rate of 97%, when we dispersed a paste by the hand ultrasonic method.

Social Distancing, Labor Supply, and Income Distribution

  • CHO, DUKSANG
    • KDI Journal of Economic Policy
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    • v.43 no.2
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    • pp.1-22
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    • 2021
  • The effects of social distancing measures on income distributions and aggregate variables are examined with an off-the-shelf heterogeneous-agent incomplete-market model. The model shows that social distancing measures, which limit households' labor supply, can decrease the labor supply of low-income households who hold insufficient assets and need income the most given their borrowing constraints. Social distancing measures can therefore exacerbate income inequality by lowering the incomes of the poor. An equilibrium interest rate can fall when the social distancing shock is expected to be persistent because households save more to prepare for rising consumption volatility given the possibility of binding to the labor supply constraint over time. When the shock is expected to be transitory, in contrast, the interest rate can rise upon the arrival of the shock because constrained households choose to borrow more to smooth consumption given the expectation that the shock will fade away. The model also shows that social distancing shocks, which diminish households' consumption demand, can decrease households' incomes evenly for every income quantile, having a limited impact on income inequality.

An engineered PD-1-based and MMP-2/9-oriented fusion protein exerts potent antitumor effects against melanoma

  • Wei, Mulan;Liu, Xujie;Cao, Chunyu;Yang, Jianlin;Lv, Yafeng;Huang, Jiaojiao;Wang, Yanlin;Qin, Ye
    • BMB Reports
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    • v.51 no.11
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    • pp.572-577
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    • 2018
  • Recent studies showed that the PD-1/PD-L1 checkpoint blockade is a dramatic therapy for melanoma by enhancing antitumor immune activity. Currently, major strategies for the PD-1/PD-L1 blockade have mainly focused on the use of antibodies and compounds. Seeking an alternative approach, others employ endogenous proteins as blocking agents. The extracellular domain of PD-1 (ePD1) includes the binding site with PD-L1. Accordingly, we constructed a PD-1-based recombinantly tailored fusion protein (dFv-ePD1) that consists of bivalent variable fragments (dFv) of an MMP-2/9-targeted antibody and ePD1. The melanoma-binding intensity and antitumor activity were also investigated. We found the intense and selective binding capability of the protein dFv-ePD1 to human melanoma specimens was confirmed by a tissue microarray. In addition, dFv-ePD1 significantly suppressed the migration and invasion of mouse melanoma B16-F1 cells, and displayed cytotoxicity to cancer cells in vitro. Notably, dFv-ePD1 significantly inhibited the growth of mouse melanoma B16-F1 tumor cells in mice and in vivo fluorescence imaging showed that dFv-ePD was gradually accumulated into the B16-F1 tumor. Also the B16-F1 tumor fluorescence intensity at the tumor site was stronger than that of dFv. This study indicates that the recombinant protein dFv-ePD1 has an intensive melanoma-binding capability and exerts potent therapeutic efficacy against melanoma. The novel format of the PD-L1-blocked agent may play an active role in antitumor immunotherapy.

Cost Reduction of Location Registration Using the LiEy UBdate Strategy in Hierarchical Mobile IPv6 (계층적 이동 Ipv6환경에서 지연갱신전략을 이용한 위치등록 비용 감소)

  • Yi Myung-Kyu;Hwang Chong-Sun
    • Journal of KIISE:Information Networking
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    • v.32 no.3
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    • pp.370-381
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    • 2005
  • Mobile IP provides an efficient and scalable mechanism for host mobility within the Internet. Using Mobile If, mobile nodes may change their point of attachment to the Internet without changing their If address. However, it would result in a high signaling cost. To reduce the signaling cost, we factor in the fact that mobile users will not be actively communicating much of the time. In fact, there Is no necessity to send a binding update message to the home agent when an mobile node does not communicates with others while moving. From this point of view, we propose a lazy update strategy for minimizing signaling cost using the forwarding pointer in hierarchical Mobile IPv6. In our proposal, binding updates are sent only when a mobile node is in a busy mode. If an mobile node is in a dormant mode, binding update messages are delayed until busy mode using the forwarding pointer. As a result, our proposal can reduce the total signaling cost by eliminating unnecessary binding update messages when a mobile node Is in a dormant mode. In addition to, our proposal reduces unnecessary location update cost resulting from ping-pong effect under mobile node's dormant mode. Analysis results using the discrete analytic model presented in this paper shows that our proposal can has superior performance than hierarchical Mobile nv6 when the call-to-mobility ratio is low and the length of the forwarding pointer chain K is low.