• Toxicological Research
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• 제26권2호
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• pp.101-108
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• 2010

Halogenated organic compounds, such as 1-bromobutane (1-BB), have been used as cleaning agents, agents for chemical syntheses or extraction solvents in workplace. In the present study, immunotoxic effects of 1-BB and its conjugation with glutathione (GSH) were investigated in female BALB/c mice. Animals were treated orally with 1-BB at 375, 750 and 1500 mg/kg in corn oil once for dose response or treated orally with 1-BB at 1500 mg/kg for 6, 12, 24 and 48 hr for time course. S-Butyl GSH was identified in spleen by liquid chromatography-electrospray ionization tandem mass spectrometry. Splenic GSH levels were significantly reduced by single treatment with 1-BB. S-Butyl GSH conjugates were detected in spleen from 6 hr after treatment. Oral 1-BB significantly suppressed the antibody response to a T-dependent antigen and the production of splenic intracellular interlukin-2 in response to Con A. Our present results suggest that 1-BB could cause immunotoxicity as well as reduction of splenic GSH content, due to the formation of GSH conjugates in mice. The present results would be useful to understand molecular toxic mechanism of low molecular weight haloalkanes and to develop biological markers for exposure to haloalkanes.

• Mass Spectrometry Letters
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• 제9권1호
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• pp.24-29
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• 2018

DC23, a triazolothione resorcinol analogue, is known to inhibit heat shock protein 90 and pyruvate dehydrogenase kinase which are up-regulated in cancer and diabetes, respectively. This study was performed to elucidate the metabolism of DC23 in human liver microsomes (HLMs). HLMs incubated with DC23 in the presence of uridine 5'-diphosphoglucuronic acid (UDPGA) and/or ${\beta}$-nicotinamide adenine dinucleotide phosphate (NADPH) resulted in the formation of four metabolites, M1-M4. M1 was identified as DC23-N-Oxide, on the basis of LC-MS/MS analysis. DC23 was further metabolized to its glucuronide conjugates (M2, M3, and M4). In vitro metabolic stability studies conducted with DC23 in HLMs revealed significant glucuronide conjugation with a $t_{1/2}$ value of 1.3 min. The inhibitory potency of DC23 on five human cytochrome P450s was also investigated in HLMs. In these experiments, DC23 inhibited CYP2C9-mediated tolbutamide hydroxylase activity with an $IC_{50}$ value of $8.7{\mu}M$, which could have implications for drug interactions.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 2002년도 학술대회지
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• pp.317-334
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• 2002

Ginsenosides are metabolized (deglycosylated) by intestinal bacteria to active forms after oral administration. 20(S)-Protopanaxadiol $20-O-{\beta}-D-glucopyranoside$ (M1) and 20(S)-protopanaxatriol (M4) are the main intestinal bacterial metabolites (IBMs) of protopanaxadiol- and protopanaxatriol-type glycosides. M1 was selectively accumulated into the liver soon after its intravenous (i.v.) administration to mice, and mostly excreted as bile; however, some M1 was transformed to fatty acid ester (EMl) in the liver. EM1 was isolated from rats in a recovery dose of approximately $24mol\%.$ Structural analysis indicated that EM1 comprised a family of fatty acid mono-esters of M1. Because EM1 was not excreted as bile as Ml was, it was accumulated in the liver longer than M1. The in vitro cytotoxicity of M1 was attenuated by fatty acid esterification, implying that esterification is a detoxification reaction. However, esterified M1 (EM1) inhibited the growth of B16 melanoma more than Ml in vivo. The in vivo antitumor activity paralleled with the pharmacokinetic behavior. In the case of M4, orally administered M4 was absorbed from the small intestine into the mesenteric lymphatics followed by the rapid esterification of M4 with fatty acids and its spreading to other organs in the body and excretion as bile. The administration of M4 prior to tumor injection abrogated the enhanced lung metastasis in the mice pretreated with 2-chloroadenosine more effectively than in those pretreated with anti-asialo GMl. Both EM1 and EM4 did not directly affect tumor growth in vitro, whereas EM1 promoted tumor cell lysis by lymphocytes, particularly non-adherent splenocytes, and EM4 stimulated splenic NK cells to become cytotoxic to tumor cells. Thus, the esterification of IBM with fatty acids potentiated the antitumor activity of parental IBM through delay of the clearance and through immunostimulation. These results suggest that the fatty acid conjugates of IBMs may be the real active principles of ginsenosides in the body.

• 대한방사성의약품학회지
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• 제7권1호
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• pp.33-40
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• 2021

Recently, antibody-drug conjugates (ADCs) are used to deliver efficient cytotoxic payloads selectively in cancer cells. In the designing of an ADC, the antibody is connected to a toxic payload via a covalent linker, which helps to solubilizes the typical hydrophobic payload as well as stabilizes the linkage over circulation. The development of the linkers for the antibody drug conjugate is still in demand. Initially, the acid, disulfide, and cathepsin-sensitive ADCs attracted considerable attention for the delivery of a potent cytotoxic payload but suffer from instability in human and mouse plasma with a short half-life. In addition, It also suffer from a solubility issue that induces aggregation, which is the major problem in their development. ADCs associated with sulfatase and phosphatase cleavable linker are highly soluble due to the anionic nature of sulfate and phosphate groups. The ADCs also showed high stability in human and mouse plasma. Therefore, to overcome these limitations, sulfatase and phosphatase cleavable linkers were developed. This review focuses on the recently reported advantages of sulfatase and phosphatase cleavable linkers for ADCs.

• Journal of applied mathematics & informatics
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• 제17권1_2_3호
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• pp.343-350
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• 2005

In this paper we prove two results about tilings of orthogonal polygons. (1) P be an orthogonal polygon with rational vertex coordinates and let R(u) be a rectangle with side lengths u and 1. An orthogonal polygon P can be tiled with similar copies of R(u) if and only if u i algebraic and the real part of each of its conjugates is positive; (2) Laczkovich proved that if a triangle $\Delta$ tiles a rectangle then either $\Delta$ is a right triangle or the angles of $\Delta$ are rational multiples of $\pi$. We generalize the result of Laczkovich to orthogonal polygons.

• Nutrition Research and Practice
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• 제2권1호
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• pp.17-21
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• 2008

Aloin is a physiologically active anthraquinone present in aloe. There are two isomers of aloin, aloin A and aloin B, occurring as a mixture of diastereomers. The objective of this study was to determine the bioavailability and tissue distribution of aloin. Rats were gavaged with 11.8g/kg aloin, and the levels of aloin and its conjugates were measured in plasma, tissues, and urine. Plasma aloin level showed a peak at 1hr after the administration and the concentration was $59.07{\pm}10.5\;ng/ml$. The 24 h cumulated urinary aloin was 0.03% of the initial dose. These results suggest that aloin is absorbed and reaches a peak plasma level within 1-1.5 h after the administration and a significant portion is possibly metabolized or is excreted in feces. These results can apply to the determination of the adequate intake level of aloe and aloe products to achieve the desired biological effect, and to interprete in vitro study results.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2001년도 추계학술발표대회
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• pp.107-110
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• 2001

Among the tested ten enzymes, Optimase M-440 showed the highest activity in transesterification of N-t-Boc-L-Phe-OTFE with D-glucose. Monosaccharides and their derivatives acted as good acyl acceptors in the Optimase M -440 catalyzed transesterification of N-t-Boc-L-Phe-OTFE. Optimase M-440 showed a preferable catalytic activity on the primary hydroxyl group of saccharides and a good regioselectivity. Optimase M-440 showed the highest activity in pyricline among the tested solvents. As acyl donors, trifluoroethyl esters of amino acids showed a high reactivity in transesterification. Optimase M-440 showed a broad substrate specificity towards amin 。 acid esters and saccharides.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2001년도 추계학술발표대회
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• pp.646-647
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• 2001

The enzymatic synthesis of conjugates of lysine and aspartic acid with D-glucose was studied. Optimase M-440 showed the very poor regioselectivity in the transesterification of $N{\alpha}$,$N'{\varepsilon}-di-t-Boc-L-Lys-OTFE$ and N-t-Boc-L-Asp-diOTFE with D-glucose. The acylation of glycosidic -OH and primary -OH of D-glucose occurred. However, Optimase M-440 catalyzed only the acylation of primary -OH group in the transesterification of $N{\alpha}$,$N'{\varepsilon}-di-t-Boc-L-Lys-OTFE$ and N-t-Boc-L-Asp-diOTFE with ${\alpha}-$ and ${\beta}-methylglucopyranoside$ in high yields without any other transesterification. Optimase M-440 also discriminated carboxyl groups of N-t-Boc-L-Asp-diOTFE.

• Natural Product Sciences
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• 제6권2호
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• pp.91-95
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• 2000

A phytochemical investigation of the aqueous ethanolic flower extract of Tamarix tetragyna led to the isolation and characterization of the hitherto unknown conjugates, kaempheride 3,7-dipotassium sulphate and kaempferol 3,4'-dipotassium sulphate as well. Twelve known flavonol compounds, including kaempheride 3-potassium sulphate and kaempheride $3-O-{\beta}-glucuronide$ were also isolated and identified. $^1H-\;and\;^{13}C-NMR$ spectra for the known kaempheride derivatives have been recorded and assigned for the first time. Structures of all compounds were established by conventional methods of analysis and confirmed by $^1H-,\;^{13}C-NMR$ and mass spectral analysis.

• 한국정밀공학회지
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• 제23권3호
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• pp.179-186
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• 2006

Single-walled carbon nanotubes (SWNT) exhibit strong Raman signals as well as fluorescence emissions in the near infrared regions where most biomolecules are transparent. Such signals do not blink or photobleach under prolonged excitation. which is advantageous to optical nano-bio marker applications. In this paper, single walled carbon nanotubes are conjugated with specific types of single-stranded DNA in order to detect oligonucleotides of corresponding complimentary sequences. Dot blotting experiments and comparative Raman spectroscopy observations demonstrated excellent sensitivity and specificity of carbon nanotube-DNA probes. The results show the possibility of using SWNT as generic nano-bio markers for the precise detection of specific kinds of genes.