• Archives of Pharmacal Research
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• 제26권12호
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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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• 제27권2호
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• pp.319-321
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• 2006

• 한국추진공학회지
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• 제2권3호
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• pp.47-53
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• 1998

Michael Reaction을 이용하여 상업적으로 이용 가능한 APS(3-aminopropyltrime thoxysilane)과 AEAPS(N-[3-(trimethoxysilyl)propyl]ethylenediamine)을 다수의 Michael acceptor(ethyl acrylate, acrylonitrile, acrylamide, 2-cyanoethyl acrylate, 2-hydroxyethyl acrylate 그리고 3-(trimethoxysilyl) propylmethacrylate)와 반응시켜 10 종류의 aminosilane[3-(N-2-carboethoxyethyl)aminopropyl]triethoxysilane, [3-(N-2-cyanoethyl)aminopropyl]triethoxysilane, [3-(N-di-2-carboethoxyethyl)aminop-ropyl]triethoxysilane, [3-(N-2-cyanoethyl)aminopropyl]triethoxysilane, [3-(N-2-cyanoethoxypropionyl)aminopropyl]triethoxysilane, [3-(N-di-2-cyanoethoxypropi-onyl) aminopropyl] triethoxysilane, [3-(N-di-2-hydroxyethoxypropionyl)aminoprop-yl]-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.

• 한국추진공학회:학술대회논문집
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• 한국추진공학회 1998년도 제11회 학술강연회논문집
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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.

• 대한화학회지
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• 제35권6호
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• pp.756-758
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• 1991

• 한국식품과학회지
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• 제41권5호
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• pp.477-482
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• 2009

TLRs는 여러 병원균들이 가지고 있는 PAMPs를 인식해서, 선천성 면역 반응을 유도하는 중요한 역할을 한다. TLR4의 이합체 형성은 신호전달 체계의 활성화와 뒤이어 발생하는 선천성 면역 반응을 유도하기 위해서 최초로 일어나는 반응으로 알려져 있다. 우리가 먹는 식품 중에는 항염증 효과가 있다고 널리 알려져 있는 phytochemicals이 포함되어 있다. 특히 ${\alpha},{\beta}$-unsaturated carbonyl group을 가지고 있는 curcumin, 6-shogaol, 그리고 cinnamaldehyde는 Michael addition 반응에 의해서 LPS에 의해서 유도된 TLR4의 이합체 형성을 억제시켜, 전사요소 NF-${\kappa}B$와 IRF3 활성화 및 그것들에 의해서 조절되는 타깃 유전자들을 억제시킨다. 이러한 결과는 ${\alpha},{\beta}$-unsaturated carbonyl group을 가지고 있는 curcumin, 6-shogaol, 그리고 cinnamaldehyde의 항염증 효능에 대한 새로운 기전을 설명해 주는 것이라 할 수 있겠다.