• Bulletin of the Korean Chemical Society
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• v.27 no.4
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• pp.484-488
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• 2006

The solid-phase synthesis of new series of 1,6,8-trisubstituted tetrahydro-2H-pyrazino[1,2-a]pyrimidine-4,7-diones as bicyclic $\beta$-turn mimetics is described. Their NF-kB inhibition activities were tested and the effect of substituents on bicyclic ring was investigated. Among the prepared compounds, the fluorobenzyl and methoxybenzyl group substituted compounds 26 and 27 at C-1 and C-8 position showed more inhibitory activities than the others. Tested at a concentration of 10 uM, these two compounds showed a 60% inhibition against the target NF kB 549.

• BMB Reports
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• v.32 no.6
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• pp.561-566
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• 1999

CA(1-8)-ME(1-12) [CA-ME], composed of cecropin A(1-8) and melittin(1-12), is a synthetic antimicrobial peptide having potent antibacterial and antitumor activities with minimal hemolytic activity. In order to investigate the effects of the flexible hinge sequence, Gly-Ile-Gly, of CA-ME on antibiotic activity, CA-ME and three analogues, CA-ME1, CA-ME2, and CA-ME3, were synthesized. The Gly-Ile-Gly sequence of Ca-ME was deleted in CA-ME1 and replaced with Pro and Gly-Pro-Gly in CA-ME2 and CA-ME3, respectively. CA-ME1 and CA-ME3 showed a significant decrease in antitumor activity and phospholipid vesicle-disrupting ability. However, CA-ME2 showed similar antitumor and vesicle-disrupting activities, as compared with CA-ME. These results suggest that the flexibility or ${\beta}$-turn induced by Gly-Ile-Gly or Pro in the central part of CA-ME may be important in the electrostatic interaction of the N-terminus cationic ${\alpha}$-helical region with the cell membrane surface and the hydrophobic interaction of the C-terminus amphipathic ${\alpha}$-helical region with the hydrophobic acyl chains in the cell membrane. CA-ME3 exhibited lower antitumor and vesicle-disrupting activities than CA-ME and CA-ME2. This result suggests that the excessive ${\beta}$-turn structure caused by the Gly-Pro-Gly sequence in CA-ME3 seems to interrupt ion channel/pore formation in the lipid bilayer. We concluded that the appropriate flexibility or bilayer. We concluded that the appropriate flexibility or ${\beta}$-turn structure provided by the central hinge is responsible for the effective antibiotic activity of the antimicrobial peptides with the helix-hinge-helix structure.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.1
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• pp.242-245
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• 2005

The most common feature of neurodegenerative disease (i.e. Alzheimer's disease, AD) is the increased number of activated microglial cells nearby the pathogenic area of the brain, such as amyloid plaque in AD. An abnormality of protein regulation and an imbalance of clearance against ${\beta}-amyloid\;(A{\beta})$ produced amyloid precursor protein (APP) can turn microglia into the activated feature out of the ramified resting phase. We examined the possibility that ginsenoside Rb1 could attenuate the microglial activation induced by massive $A{\beta}$ that has known to induce a chronic inflammation, which is a major cause of AD by damaging neuronal cells (i.e. apoptosis or necrosis). Aggregated $A{\beta}42\;(5\;{\mu}M)$ peptide was used with lipopolysaccharide (LPS) ($10\;{\mu}g$) for a comparative control up to 48hours. We found that Rb1 reduced the production of nitric oxide as well as proinflammatory cytokines, such as $IL-1{\beta}$ and $TNF-{\alpha}$.

• International Journal of Oral Biology
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• v.41 no.4
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• pp.237-242
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• 2016

Interleukin-1b ($IL-1{\beta}$), a proinflammatory cytokine, regulates the innate immune responses against bacterial infection. Mature $IL-1{\beta}$ is produced from $pro-IL-1{\beta}$ by activated caspase-1, which in turn is activated by the inflammasome complex formation. In this study, we compared the inflammasome mRNA expression induced by S. sanguinis, S. oralis, F. nucleatum and P. intermedia. Among the tested bacteria, S. sanguinis induced the highest $IL-1{\beta}$ secretion. S. oralis, F. nucleatum and P. intermedia induced very weak $IL-1{\beta}$ secretion. S. sanguinis mostly induced the NLRP3 mRNA expressions. Although F. nucleatum did not induce high $IL-1{\beta}$ secretion, it induced high expression levels of AIM2, NLRP2, and NLRP3. No specific inflammasomes were induced by S. oralis and P.intermedia. Studying the inflammasome complex activation induced by oral bacteria may thus enhance our understanding of the pathogenesis of oral diseases.

• Bulletin of the Korean Chemical Society
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• v.11 no.1
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• pp.49-54
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• 1990

The gas-phase thermolysis reactions of ${\alpha}$- and ${\beta}$-methylated ethyl formates, Y = $CH-X-CHR_1CH_2R_2$ where X = Y = O or S and $R_1\;=\;R_2$ = H or $CH_3$, are investigated theoretically using the AM1 method. The experimental reactivity order is reproduced correctly by AM1 in all cases. The thermolysis proceeds through a six-membered cyclic transition state conforming to a retro-ene reaction, which can be conveniently interpreted using the frontier orbital theory of three-species interactions. The methyl group substituted at $C_{\alpha}\;or\;C_{\beta}$ is shown to elevate the ${\pi}$-HOMO of the donor fragment (Y = C) and depress the ${\sigma}^{\ast}$-LUMO of the acceptor fragment ($C_{\beta}$-H), increasing the nucleophilicity of Y toward ${\beta}$-hydrogen which in turn increases the reactivity. The two bond breaking processes of the $C_{\alpha}$-X and $C_{\beta}$-H bonds are concerted but not synchronous so that the reaction takes place in two stages as Taylor suggested. The initial cleavage of $C_{\alpha}$-X is of little importance but the subsequent scission of $C_{\beta}$-H occurs in a rate determining stage.

• Food Science and Biotechnology
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• v.18 no.1
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• pp.271-274
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• 2009

Cereal $\beta$-glucans, linked essentially by mixed $\beta$-(1,4/1,3) glycosidic bonds, were extracted, purified, and structurally identified. Previously chemical structure of barley $\beta$-glucans was characterized from 3 varieties of 'Gang', 'Ohl', and 'Gwangan', and the (1,4)/(1,3) linkage ratio of the $\beta$-glucans was identical. In this study, $\beta$-glucans from 1 barley ('Chal') and 3 oat ('Ohl', 'Samhan', and 'Donghan') varieties were structurally scrutinized, and the linkage pattern of total 7 cereal $\beta$-glucans was compared. The amount of 2 major 3-O-$\beta$-cellobiosyl-D-glucose (DP3) and 3-O-$\beta$-cellotriosyl-D-glucose (DP4) from barley and oat accounted for only 66.6-73.3 and 68.12-81.89% of water-extractable $\beta$-glucan fractions, and the (1,4)/(1,3) linkage ratios of both barley and oat $\beta$-glucans were within very narrow range of 2.27-2.31 and 2.38-2.39, respectively, among the cultivars tested. Structural difference in the cereal $\beta$-glucans was evident when DP3:DP4 ratio in the $\beta$-glucan structure was compared. As a result, this ratio was significantly greater for barley $\beta$-glucan (2.26-2.74) than for oat (1.54-1.66). Chal-B had the greatest DP3 to DP4 ratio among the samples, which in turn reflected the least amount of (1,4)-linkages.

• Molecules and Cells
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• v.28 no.1
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• pp.25-30
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• 2009

${\beta}$-Arrestins turn off G protein-mediated signals and initiate distinct G protein-independent signaling pathways. We previously demonstrated that angiotensin $AT_1$ receptorbound ${\beta}$-arrestin 1 is cleaved after $Phe^{388}$ upon angiotensin II stimulation. The mechanism and signaling pathway of angiotensin II-induced ${\beta}$-arrestin cleavage remain largely unknown. Here, we show that protein Tyr phosphatase activity is involved in the regulation of ${\beta}$-arrestin 1 cleavage. Tagging of green fluorescent protein (GFP) either to the N-terminus or C-terminus of ${\beta}$-arrestin 1 induced conformational changes and the cleavage of ${\beta}$-arrestin 1 without angiotensin $AT_1$ receptor activation. Orthovanadate and molybdate, inhibitors of protein Tyr phosphatase, attenuated the cleavage of C-terminal GFP-tagged ${\beta}$-arrestin 1 in vitro. The inhibitory effects of okadaic acid and pyrophosphate, which are inhibitors of protein Ser/Thr phosphatase, were less than those of protein Tyr phosphatase inhibitors. Cell-permeable pervanadate inhibited angiotensin II-induced cleavage of ${\beta}$-arrestin 1 in COS-1 cells. Our findings suggest that Tyr phosphorylation signaling is involved in the regulation of angiotensin II-induced ${\beta}$-arrestin cleavage.

• Animal cells and systems
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• v.5 no.4
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• pp.267-274
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• 2001

Calpains are a family of cysteine proteases existing primarily in two forms designated by the $Ca^{2+}$ concentration needed for activation in vitro, $\mu$-calpain (calpain-I) and m-calpain (calpain-II). The physiologica1 roles of calpains remain unclear. Many groups have proposed a role for calpains In apoptosis, but their patterns of activation are not well characterized. Calpains have been implicated in neutrophil apoptosis, glucocorticoid-induced thymocyte apoptosis, as well as many other apoptotic pathways. Calpain activation in apoptosis is usually linked upstream or downstream to caspase activation, or in a parallel pathway alongside caspase activation. Calpains have been suggested to be involved in DNA fragmentation (via endonuclease activation), but also as effector proteases that cleave cellular proteins involved in DNA repair, membrane associated proteins and other homeostatic regulatory proteins. Recently, our laboratory demonstrated $\mu$-calpain activation in NAD(P)H: quinone oxidoreducatse 1 (NQO1)-expressing cells after exposure to $\beta$-lapachone, a novel quinone and potential chemo- and radio-therapeutic agent. Increased cytosolic $Ca^{2+}$ in NQO1-expressing cells after $\beta$-lapachone exposures were shown to lead to $\mu$-calpain activation. In turn, $\mu$-calpain activation was important for substrate proteolysis and DNA fragmentation associated with apoptosis. Upon activation, $\mu$-calpain translocated to the nucleus where it could proteolytically cleave PARP and p53. We provided evidence that $\beta$-lapachone-induced, $\mu$-calpain stimulated, apoptosis did not involve any of the known caspases; known apoptotic caspases were not activated after $\beta$-lapachone treatment of NQO1-expressing cells, nor did caspase inhibitors have any effect on $\beta$-1apachone-induced cell death. Elucidation of processes by which $\beta$-1apachone-stimulated $\mu$-calpain activation and calpains ability to activate endonucleases and induce apoptosis independent of caspase activity will be needed to further develop/modulate $\beta$-lapachone for treatment of human cancers that over-express NQO1.

• Bulletin of the Korean Chemical Society
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• v.34 no.5
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• pp.1401-1406
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• 2013

This study tested the feasibility of observing H/D exchange of intact protein by top-down electron capture dissociation (ECD) mass spectrometry for the investigation of protein structure. Ubiquitin is selected as a model system. Local structural information was obtained from the deuteration levels of c and $z^{\cdot}$ ions generated from ECD. Our results showed that ${\alpha}$-helix region has the lowest deuteration level and the C-terminal fraction containing a highly mobile tail has the highest deuteration level, which correlates well with previous X-Ray and HDX/NMR analyses. We studied site-specific H/D exchange kinetics by monitoring H/D exchange rate of several structural motives of ubiquitin. Two hydrogen bonded ${\beta}$-strands showed similar HDX rates. However, the outer ${\beta}$-strand always has higher deuteration level than the inner ${\beta}$-strand. The HDX rate of the turn structure (residues 8-11) is lower than that of ${\beta}$-strands (residues 1-7 and residues 12-17) it connects. Although isotopic distribution gets broader after H/D exchange which results in a limited number of backbone cleavage sites detected, our results demonstrate that this method can provide valuable detailed structural information of proteins. This approach should also be suitable for the structural investigation of other unknown proteins, protein conformational changes, as well as protein-protein interactions and dynamics.

• Restorative Dentistry and Endodontics
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• v.34 no.5
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• pp.415-423
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• 2009

The purpose of this study is to investigate the response of human pulp cell on Portland cement mixed with $\beta$-glycerophosphate. To investigate the effect of $\beta$-glycerophosphate and/or dexamethasone on human pulp cell, ALP activity on various concentration of $\beta$-glycerophosphate and dexamethasone was measured and mineral nodule of human pulp cell was stained with Alizarin red S. MTS assay and ALP activity of human pulp cell on Portland cement mixed with various concentration of $\beta$-glycerophosphate (10 mM, 100mM, 1M) was measured and the specimens were examined under SEM. Addition of $\beta$-glycerophosphate or dexamethasone alone had no effect however, the addition of 5 mM $\beta$-glycerophosphate and 100 nM dexamethasone had the largest increasement in ALP activity. There was no toxicity in all samples and the data showed that Portland cement mixed with 10 mM $\beta$-glycerophosphate had more increase in ALP activity compared with control. In conclusion, Portland cement mixed with $\beta$-glycerophosphate has no toxicity and promotes differentiation and mineralization of pulp cell compared with additive-free Portland cement. This implicated that application of Portland cement mixed with $\beta$-glycerophosphate might form more reparative dentin and in turn it would bring direct pulp capping to success.