• Bulletin of the Korean Chemical Society
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• v.35 no.8
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• pp.2494-2504
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• 2014

P38 mitogen activated protein (MAP) kinase is an important anti-inflammatory drug target, which can be activated by responding to various stimuli such as stress and immune response. Based on the conformation of the conserved DFG loop (in or out), binding inhibitors are termed as type-I and II. Type-I inhibitors are ATP competitive, whereas type-II inhibitors bind in DFG-out conformation of allosteric pocket. It remains unclear that how these allosteric inhibitors stabilize the DFG-out conformation and interact. Organosilicon compounds provide unusual opportunity to enhance potency and diversity of drug molecules due to their low toxicity. However, very few examples have been reported to utilize this property. In this regard, we performed docking of an inhibitor (BIRB) and its silicon analog (Si-BIRB) in an allosteric binding pocket of p38. Further, molecular dynamics (MD) simulations were performed to study the dynamic behavior of the simulated complexes. The difference in the biological activity and mechanism of action of the simulated inhibitors could be explained based on the molecular mechanics/generalized Born surface area (MM/GBSA) binding free energy per residue decomposition. MM/GBSA showed that biological activities were related with calculated binding free energy of inhibitors. Analyses of the per-residue decomposed energy indicated that van der Waals and non-polar interactions were predominant in the ligand-protein interactions. Further, crucial residues identified for hydrogen bond, salt bridge and hydrophobic interactions were Tyr35, Lys53, Glu71, Leu74, Leu75, Ile84, Met109, Leu167, Asp168 and Phe169. Our results indicate that stronger hydrophobic interaction of Si-BIRB with the binding site residues could be responsible for its greater binding affinity compared with BIRB.

• Development and Reproduction
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• v.7 no.2
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• pp.69-80
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• 2003

The zebrafish(Danio rerio) is a pre-eminent vertebrate model system for clarification of the roles of specific genes and signaling pathways in development. We show examples of positional cloning in two developmental mutants in zebrafish. headless: The severe head defects in headless(hdl) mutants are due to a mutation in T-cell factor-3(Tcf3). Loss of Tcf3 function in the hdl mutant reveals that Hdl represses Wnt target genes. The results provide genetic evidence that a component of the Wnt signaling pathway is essential in vertebrate head formation and patterning. mind bomb: Reduced lateral inhibition in mind bomb(mib) mutants permits too many neural precursors to differentiate as neurons. Positional cloning of mib revealed that it is a gene in the Notch pathway that encodes a ubiquitin E3 ligase. Mib interacts with the intracellular domain of Delta to promote its internalization. The results suggest a model for Notch activation where the Delta-Notch interaction is followed by endocytosis of Delta and transendocytosis of the Notch extracellular domain by the signaling cell.

• Applied Chemistry for Engineering
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• v.3 no.1
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• pp.46-52
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• 1992

$TiO_2/SO_4{^{2-}}$ was prepared by precipitation from the mixed solution of titanium chloride and hydrochloric acid followed by modification with sulfuric acid. The characterization of prepared catalyst was performed by using IR, XPS, XRD and DT-TGA. Infrared spectra of $TiO_2/SO_4{^{2-}}$ showed bidentate sulfate ion coordinated to the surface of $TiO_2$. The acid strength of modified catalyst was at least $H_0{\leq}-14.52$, showing the superacidic properties which are attributed to the double bond nature of S=O of the complex formed by the interaction of $TiO_2$ with sulfate ion. For $TiO_2/SO_4{^{2-}}$, the specific surface area increased and the transition from the amorphous to anatase phase occurred at a higher temperature, as compared with pure $TiO_2$.

• Toxicological Research
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• v.31 no.1
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• pp.11-16
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• 2015

Our body's immune system has defense mechanisms against pathogens such as viruses and bacteria. Immune responses are primarily initiated by the activation of toll-like receptors (TLRs). In particular, TLR4 is well-characterized and is known to be activated by gram-negative bacteria and tissue damage signals. TLR4 requires myeloid differentiation factor 2 (MD2) as a co-receptor to recognize its ligand, lipopolysaccharides (LPS), which is an extracellular membrane component of gram-negative bacteria. Gambogic acid is a xanthonoid isolated from brownish or orange resin extracted from Garcinia hanburyi. Its primary effect is tumor suppression. Since inflammatory responses are related to the development of cancer, we hypothesized that gambogic acid may regulate TLR4 activation. Our results demonstrated that gambogic acid decreased the expression of pro-inflammatory cytokines ($TNF-{\alpha}$, IL-6, IL-12, and $IL-1{\beta}$) in both mRNA and protein levels in bone marrow-derived primary macrophages after stimulation with LPS. Gambogic acid did not inhibit the activation of Interferon regulatory factor 3 (IRF3) induced by TBK1 overexpression in a luciferase reporter gene assay using IFN-${\beta}$-PRD III-I-luc. An in vitro kinase assay using recombinant TBK1 revealed that gambogic acid did not directly inhibit TBK1 kinase activity, and instead suppressed the binding of LPS to MD2, as determined by an in vitro binding assay and confocal microscopy analysis. Together, our results demonstrate that gambogic acid disrupts LPS interaction with the TLR4/MD2 complex, the novel mechanism by which it suppresses TLR4 activation.

• Reproductive and Developmental Biology
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• v.36 no.2
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• pp.121-131
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• 2012

After spermatogenesis, spermatozoa come in contact with fluids in the epididymis where they mature. During ejaculation, spermatozoa are mixed with secretions from prostate gland, vesicular glands, and bulbourethral glands. During natural mating, seminal plasma is deposited in the female reproductive tract eliciting various physiological and immunological responses. With the advances in proteomics, the components of seminal plasma have been identified and the information may be valuable in identifying markers for fertility. Components of seminal plasma that affect fertility have been discovered and the mechanism of action of these factors has been determined. The objective of this study was to determine the specific seminal plasma proteins from Korean native cattle, Hanwoo, and Korean native brindle cattle (KNBC) with the long term goal of improving fertilization rate. After SDS-PAGE and 2-dimensional gel electrophoresis, proteins were identified by Q-ToF analysis. They include plasma serine protease inhibitor precursor and platelet-activating factor acetylhydrolase after SDS-PAGE. Number and density of the spots in 2-dimensional gels were higher in KNBC than Hanwoo. Proteins identified from the paired spots of both breeds include chain A, bull seminal plasma PDC-109 Fibronectin Type II module, BSP-30 kDa precursor, and Spermadhesin Z13 or its precursor. Interestingly, some proteins were identified from multiple spots. The functional differences of these diverse forms of the proteins may require further studies. With their previously reported roles in sperm capacitation by these proteins, the studies on the mechanism of action, ligand interaction and the variation in the genome may help improving fertility in cattle.

• Journal of Life Science
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• v.18 no.3
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• pp.298-303
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• 2008

Using a phage peptide library approach, we have isolated a peptide ligand that binds to transferrin receptor on the surface of human melanoma cell, B16F10. The library was first screened twice by recovering internalized phages and was further screened three times by competitively eluting transferrin receptor-specific phages with human transferrin among the phages bound to the cell surface. The peptides displayed by the selected phages were fused to translocation and catalytic domain of Pseudomonas exotoxin to prepare recombinant toxins. After estimating cytotoxicity of each recombinant toxin toward B16F10 cell, seven clones were selected. Sequence analysis revealed that one of the clones displayed a peptide which had a significant sequence homology with human transferrin. The peptide was chemically synthesized and was shown to be functional in delivering cytotoxic agents into B16F10 cell via interaction with transferrin receptor.

• Journal of the Korean Chemical Society
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• v.37 no.4
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• pp.442-447
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• 1993

The thermodynamic parameters (${\Delta}$G, ${\Delta}$H and ${\Delta}$S) of lanthanides(III)-benzoylformate complexes in aqueous solution have been determined in the ionic medium of 0.1M $NaClO_4$ at 25$^{\circ}C$, using pH and enthalpy titration method. The stability constants of the lanthanide(III)-benzoylformate complexes (1 : 1) agree well with the general relationships for the bidentate ligands (e.g., log${\beta}_1$ vs. p$K_a$). Thermodynamic evidences show that the oxygen atom in ketone group is coordinated along with the carboxylate group. It is ascribed to the increasing charge density on the oxygen atom in ketone group due to the conjugation effect in the benzoylformate ligand. Thermodynamic results also indicate that the complexes are stabilized by the enthalpy effect caused by the ionic interaction of metal-oxygen bond as well as the entropy effect.

• Bulletin of the Korean Chemical Society
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• v.33 no.4
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• pp.1303-1309
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• 2012

A novel ligand N,N'-(2,6-pyridinedicarbonyl)bis[N-(carboxymethyl)] (L1) was designed and synthesized. Four co-luminescence groups of Sm-La-pyridyl carboxylic acids systems were researched, which are $K_4Sm_{(1-x)}-La_x(L_1)Cl_3{\cdot}y_1H_2O$, $K_4Sm_{(1-x)}La_x(L_2)Cl_3{\cdot}y_2H_2O$, $K_6Sm_{2(1-x)}La_{2x}(L_3)Cl_6{\cdot}y_3H_2O$, $K_4Sm_{(1-x)}La_x(L_4)Cl_3{\cdot}y_4H_2O$. The results indicated the addition of La(III) could sensitize the luminescence of Sm(III) obviously in a certain range, enhancing emission intensity of Sm-pyridyl carboxylic acids relative to the undoped ones. The optimal mole percentages of La(III) in the mixed ions for $L_1$, $L_2$, $L_3$, $L_4$ were confirmed to be 0.6, 0.5, 0.3, 0.6, respectively. The mechanism of the fluorescence enhancement effect was discussed in detail. Furthermore, the binding interaction of $K_4Sm_{0.4}La_{0.6}(L_4)Cl_3{\cdot}5H_2O$ with bovine serum albumin (BSA) have been investigated due to its potential biological activity. The binding site number n was equal to 1.0 and binding constant $K_a$ was about $2.5{\times}10^5\;L{\cdot}mol^{-1}$.

• Bulletin of the Korean Chemical Society
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• v.34 no.2
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• pp.600-608
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• 2013

Amide analogs of tridecapeptide ${\alpha}$-factor (WHWLQLKPGQPMYCONH$_2$) of Saccharomyces cerevisiae, in which Trp at position 1 and 3 were replaced with other residues, were synthesized to ascertain whether cooperative interactions between two Trp residues occurred upon binding with its receptor. Analogs containing Ala or Aib at position 3 of the peptide $[Ala_3]{\alpha}$-factor amide (2) and $[Aib_3]{\alpha}$-factor amide (5) exhibited greater decreases in bioactivity than analogs with same residue at position one $[Ala^1]{\alpha}$-factor amide (1) and $[Aib^1]{\alpha}$-factor amide (4), reflecting that $Trp^3$ may plays more important role than $Trp^1$ for agonist activity. Analogs containing Ala or Aib in both position one and three 3, 6 exhibited complete loss of bioactivity, emphasizing both the essential role and the combined role of two indole rings for triggering cell signaling. In contrast, double substituted analog with D-Trp in both positions 9 exhibited greater activity than single substituted analog with D-Trp 8 or deleted analog 7, reflecting the combined contribution of two tryptophane residues of ${\alpha}$-factor ligand to activation of Ste2p through interaction with residue $Tyr^{266}$ and importance of the proper parallel orientation of two indole rings for efficient triggering of signal G protein coupled activation. Among ten amide analogs, $[Ala^{1,3}]{\alpha}$-factor amide (3), $[Aib^{1,3}]{\alpha}$-factor amide (6), [D-$Trp^3]{\alpha}$-factor amide (8) and [des-$Trp^1,Phe^3]{\alpha}$-factor amide (10) were found to have antagonistic activity. Analogs 3 and 6 showed greater antagonistic activity than analogs 8 and 10.

• Journal of the Korean Chemical Society
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• v.42 no.4
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• pp.443-448
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• 1998

The thermodynamic parameters for the interaction of metal ions with dibenzo-16-crown-5 and its derivatives have been determined by solution calorimetry in methanol at 25$^{\circ}C$. Thermodynamic properties of log K, ${\Delta}H$, and $T{\Delta}S$ have been determined for the complexation of metal cations by dibenzo-16-crown-5 and its derivatives. Dibenzo-16-crown-5 and its derivatives have been studied as metal cations carrier in bulk liquid membrane (BLM) and supported liquid membrane (SLM) system. $Ag^+$ has been much more transported using dibenzo-16-crown-5 derivatives as carriers and several other metal cations have been small transported using carrier in BLM and SLM system. Ligand structure, the length of side arm, donor atom, stability constant, and carrier concentration are also important parameters in the transport of cations.