• Archives of Pharmacal Research
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• v.26 no.12
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• pp.1047-1054
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• 2003

Molecular chaperones have a crucial role in the folding of nascent polypeptides in endoplasmic reticulum. Some of them are known to be sensitive to the modification by electrophilic metabolites of organic pro-toxicants. In order to identify chaperone proteins sensitive to alkyators, ER extract was subjected to alkylation by 4-acetamido-4 -maleimidyl-stilbene-2,2 -disulfonate (AMS), and subsequent SDS-PAGE analyses. Protein spots, with molecular mass of 160, 100, 57 and 36 kDa, were found to be sensitive to AMS alkylation, and one abundant chaperon protein was identified to be protein disulfide isomerase (PDI) in comparison with the purified PDI. To see the reactivity of PDI with cysteine alkylators, the reduced form ($PDI_{red}$) of PDI was incubated with various alkylators containing Michael acceptor structure for 30 min at $38^{\circ}C$ at pH 6.3, and the remaining activity was determined by the insulin reduction assay. Iodoacetamide or N-ethylmaleimide at 0.1 mM remarkably inactivated $PDI_{red}$ with N-ethylmaleimide being more potent than iodoacetamide. A partial inactivation of $PDI_{oxid}$ was expressed by iodoacetamide, but not N-ethylmaleimide (NEM) at pH 6.3. Of Michael acceptor compounds tested, 1,4-benzoquinone ($IC_{50}, 15 \mu$ M) was the most potent, followed by 4-hydroxy-2-nonenal and 1,4-naphthoquinone. In contrast, 1,2-naphthoquinone, devoid of a remarkable inactivation action, was effective to cause the oxidative conversion of $PDI_{red}$ to $PDI_{oxid}$. Thus, the action of Michael acceptor compounds differed greatly depending on their structure. Based on these, it is proposed that POI, one of chaperone proteins in ER, could be susceptible to endogenous or xenobiotic Michael acceptor compounds in vivo system.

• Bulletin of the Korean Chemical Society
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• v.27 no.2
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• pp.319-321
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• 2006

• Journal of the Korean Society of Propulsion Engineers
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• v.2 no.3
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• pp.47-53
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• 1998

Using Michael Reaction, commercially available 3-aminopropyltrimethoxysilane and N-[3-(trimethoxysilyl)propuyl]ethylenediamine were reacted with various Michael acceptors, ethyl acrylate, acrylonitrile, acrylamide, 2-cyanoethyl acrylate, 2-hydroxyethyl acrylate and 3-(trimethoxysilyl)propylmethacrylate, to the new aminosilanes. All compounds which are [3-(N-2-carboethoxyethyl)aminopropyl]triethoxysilane, [3-(N-2-cyanoethyl)aminopropyl]triethoxysilane, [3-(N-di-2-car-boethoxyethyl)aminopropyl]triethoxysilane, [3-N-di-cyanoethyl) aminopropyl]triethoxysilane, [3-(N-2-cyanoethoxypropionyl)aminopropyl]triethoxysilane, [3-(N-di-2-cyanoethoxypropionyl)aminopropyl]triethoxysilane, [3-(N-di-2-hydroxyethoxy propionyl)aminopropyl]triethoxysilane, [3-(N-2-amidoethyl)aminopropyl]triethoxysil-ane,｛3-[N-(N-di-2-cyanoethyl)ethyl]aminopropyl｝triethoxysilane and ｛3-[N-(3-trimethoxysilylpropyl)-2-methylpropionyl]aminopropyl｝triethoxysilane were succes-sfully prepared in 35-70% yields and which were identified with $^1{H}$-NMR and FT-IR spectroscopy.

• Proceedings of the Korean Society of Propulsion Engineers Conference
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• 1998.10a
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• pp.23-23
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• 1998

Michael Reaction을 이용하여 상업적으로 이용 가능한 APS(3-aminopropyltrime thoxysilane)과 AEAPS(N-[3-(trimethoxysilyl)propy1] ethylenediamine)을 다수의 Michael acceptor(ethyl acrylate, acrylonitrile, acrylamide, 2-cyanoethyl acrylate, 2-hydroxyethyl acrylate 그리고 3-(trimethoxysilyl)propylmethacrylate)와 반응시켜 10종류의 aminosilane ([3-｛N-2-carboethoxyethyl)aminopropyl]triethoxysilane, [3-(N-2-cyanoethyl)aminopropyl] triethoxysilane, [3-(N-di-2-carboethoxyethyl) aminopropyl]triethoxysilane, [3-(N-di-2-cyanoethyl)aminopropyl]triethoxysilane, [3-(N-2-cyanoethoxypropionyl)aminopropyl] triethoxysilane, [3-(N-di-2-cyanoethoxypropionyl)aminopropyl] triethoxysilane, [3-(N-di-2-hydroxyethoxypropionyl) aminopropyl]-triethoxysilane, [3-(N-2-amidoethyl aminopropyl]triethoxysilane, ｛3-[N-(N-di-2-cyanoethyl)ethyl]aminopropyl)triethoxysilane, ｛3-[N-(3-trimethoxy-silylpropyl)-2-methylpropionyl]aminopropyl)triethoxysilane 등을 35-70% 수율로 제조하였으며, 이들의 구조는 $^1$H-NMR과 FT-IR spectroscopy를 이용하여 확인하였다.

• Journal of the Korean Chemical Society
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• v.35 no.6
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• pp.756-758
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• 1991

• Korean Journal of Food Science and Technology
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• v.41 no.5
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• pp.477-482
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• 2009

Toll-like receptors (TLRs) play a critical role in the induction of innate immune responses that are essential for host defense against invading microbial pathogens. In general, TLRs have two major downstream signaling pathways, namely MyD88- and TRIF-dependent pathways, leading to the activation of nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and interferon regulatory factor 3 (IRF3) and the expression of inflammatory mediators. TLR4 dimerization is required for the activation of downstream signaling pathways and may be one of the first lines of regulation in activating TLR-mediated signaling pathways. In this paper, the molecular targets of curcumin, 6-shogaol, and cinnamaldehyde in TLR signaling pathways will be discussed. Curcumin, 6-shogaol, and cinnamaldehyde with ${\alpha},{\beta}$-unsaturated carbonyl groups inhibit the dimerization of TLR4 induced by lipopolysaccharide, resulting in the downregulation of NF-${\kappa}B$ and IRF3. These results suggest that phytochemicals with the structural motif conferring Michael addition inhibit TLR4 dimerization, suggesting a novel mechanism for the anti-inflammatory activity of phytochemicals.