• Title/Summary/Keyword: Conjugate addition

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Synthesis, Characterization and In Vitro Evaluation of Triptolide-lysozyme Conjugate for Renal Targeting Delivery of Triptolide

  • Zheng, Qiang;Gong, Tao;Sun, Xun;Zhang, Zhi-Rong
    • Archives of Pharmacal Research
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    • v.29 no.12
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    • pp.1164-1170
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    • 2006
  • A triptolide-lysozyme (TP-LZM) conjugate was synthesized to achieve renal specific delivery and to reduce the side effects of triptolide. Triptolide was coupled to lysozyme through succinic via an ester bond with an average coupling degree of 1 mol triptolide per 1 mol lysozyme. The lysozyme can specifically accumulate in the proximal tubular cells of the kidney, making it a potential carrier for targeting drugs to the kidney. The structure of triptolide succinate (TPS) was confirmed by IR, $^{1}H-NMR$, MS and UV. The concentrations of triptolide in various samples were determined by reversed-phase high-performance liquid chromatography (HPLC). In this study, the physicochemical and stability profiles of TP-LZM under various conditions were investgated the stability and releasing profiles of triptolide-lysozyme (TP-LZM) under various conditions. In vitro release trails showed triptolide-lysozyme was relatively stable in plasma (less than 30% of free triptolide released) and could release triptolide quickly in lysosome (more than 80% of free triptolide released) at $37^{\circ}C$ for 24 h. In addition, the biological activities of the conjugate on normal rat kidney proximal tubular cells (NRK52E) were also tested. The conjugate can effectively reduce NO production in the medium of NRK52E induced by lipopolysaccharide (LPS) but with much lower toxicity. These studies suggest the possibility to promote curative effect and reduce its extra-renal toxicity of triptolide by TP-LZM conjugate.

The Estimation of an Origin-Destination Matrix from Traffic Counts using Conjugate Gradient Method in Nationwide Networks (관측교통량 기반 기종점 OD행렬 추정모형의 대규모 가로망에 적용(CG모형 적용을 중심으로))

  • Lee, Heon-Ju;Lee, Seung-Jae
    • Journal of Korean Society of Transportation
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    • v.23 no.3 s.81
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    • pp.61-71
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    • 2005
  • We evaluated the availability of Origin-Destination Matrix from traffic counts Using conjugate gradient method to large scale networks by applying it to the networks in 246 zones. As a result of the analysis of the consistency of the model on Nationwide Networks, the upper and lower levels in model had the systematic relationship internally. From the analysis of the estimable power or the model according to the number of traffic counting links, the error in traffic volume had the estimable power in the range of permissible error. In addition, the estimable power of estimation of an Origin-Destination Matrix was more satisfactory than that of existing methods. We conclude that conjugate gradient method cab be applied to nationwide networks if we can make sure that the algorithm of the developed model is reliable by doing various kinds of experiment.

Image Coding Using LOT and FSVQ with Two-Channel Conjugate Codebooks (LOT와 2-채널 결합 코드북을 갖은 FSVQ를 이용한 영상 부호화)

  • 채종길;황찬식
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.19 no.4
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    • pp.772-780
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    • 1994
  • Vector quantization with two-channel conjugate codebook has been researched as an efficient coding technique that can reduce the computational complexity and codebook storage. This paper proposes FSVQ using two-channel conjugate codebook in order to reduce the number of state codebooks. Input vector in the two-channel conjugate FSVQ is coded with state codebook of a seperated state according to each codebook. In addition, LOT is adopted to obtain to obtain a high coding gain and to reduce blocking effect which appears in the block coding. As a result, although FSVQ can achieve higher data compression ratio than general vector quantization, it has a disadvantage of having a very large number of state codebooks. However FSVQ with two-channel conjugate codebooks can employ a significantly reduced number of state codebooks, even though it has a small loss in the PSNR compared with the conventional FSVQ using one codebook. Moreover FSVQ in the LOT domain can reduce blocking effect and high coding gain compared with FSVQ in the spatial domain.

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A study on the improvement of the local stress field in a displacement-formulated finite element solution (변위형 유한요소 해에서 국부응력장 향상에 대한 연구)

  • Song, Kee-Nam
    • Transactions of the Korean Society of Mechanical Engineers A
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    • v.22 no.2
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    • pp.278-288
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    • 1998
  • An efficient and useful method to improve the local stress field in a displacement-formulated finite element solution has been proposed using the theory of conjugate approximations for a stress field and the Loubignac's iterative method for a displacement field. Validity of the proposed method has been tested through three test examples, to improve the stress field and displacement field in the whole domain and the local regions. As a result of analysis on the test examples, it is found that the stress field in the local regions are approximated to those in the whole domain within a few iterations which have satisfied the original finite element equilibrium equation. In addition, it is found that the local stress field are by far better approximated to the exact stress field than the displacement-based stress field with the reduction of the finite-element mesh-size.

Silk Fibroin/Chitosan Conjugate Crosslinked by Tyrosinase

  • Kang, Gyung-Don;Lee, Ki-Hoon;Ki, Chang-Seok;Nahm, Joong-Hee;Park, Young-Hwan
    • Macromolecular Research
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    • v.12 no.5
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    • pp.534-539
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    • 2004
  • Two biopolymers, silk fibroin (SF) and chitosan, were conjugated by tyrosinase (EC 1.14.18.1), a polyphenolic oxidase, to improve their physicochemical properties, such as their thermal properties and morphological stabilities in organic solvents. The crosslinking between SF and chitosan took place mainly through Michael addition reactions. A main reaction between the amino groups in chitosan and o-quinone, the oxidation product of the tyrosyl residue in SF, was confirmed by UV spectroscopy. Measurements of viscosity and light scattering indicated that the crosslinked SF/chitosan conjugate was compact: it had a smaller particle size because of tight bonding forces between the SF and chitosan molecular chains. Thermal decomposition of SF/chitosan conjugates crosslinked by tyrosinase occurred at higher temperatures. The adhesiveness of the SF/chitosan conjugates decreased steadily as the crosslinking reaction progressed. We propose that this new crosslinking method be used for the preparation of silk fibroin/chitosan conjugates using tyrosinase. We expect that SF/chitosan conjugates crosslinked by tyrosinase can be used preferentially in biomedical applications because of its unique properties and non-toxicity.

Exploration of Essential Structure of Malloapelta B for the Inhibitory Activity Against TNF Induced $NF-{\kappa}B$ Activation

  • Luu, Chinh Van;Chau, Minh Van;Lee, Jung-Joon;Jung, Sang-Hun
    • Archives of Pharmacal Research
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    • v.29 no.10
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    • pp.840-844
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    • 2006
  • For the exploration of pharmacophoric moiety of malloapelta B (1) possessing the inhibitory activity of $NF-{\kappa}B$ activation, structural variation of ${\alpha},{\beta}-unsaturated$ carbonyl motif was attempted. 1 was reduced by catalytic hydrogenation, sodium borohydride, and lithium aluminumhydride. Catalytic hydrogenation with 30 psi or 15 psi of $H_2$ gas of 1 generated 8-butyl-5,7-dimethoxy-2,2-dimethylchroman (2) and 1-(5,7-dimethoxy-2,2-dimethylchroman-8-yl)butan-1-one (3), respectively. Reduction with sodium borohydride occurred at the double bond of ${\alpha},{\beta}-unsaturated$ ketone of 1 to give 1-(5,7-dimethoxy-2,2-dimethyl-2H-chromen-8-yl)butan-1-one (4). Reduction of 1 with lithium aluminumhydride and then quenched with methanol and water produced unexpected products, 1-(5,7-dimethoxy-2,2-dimethyl-2H-chromen-8-yl)-3-methoxy-1-butene (5) and 1-(5,7-dimethoxy-2,2-dimethyl-2H-chromen-8-yl)-3-hydroxy-1-butene (6). These are formed from the isomerization of initial product 9 through the continuous conjugate carbocation intermediate 11. Addition of ethylmagnesium bromide and dimethyl malonate anion to 1 gave the conjugate adducts 7 and 8. Ethylmagesium bromide and sodium borohydride reduction unusually gave the conjugate addition due to steric congestion around carbonyl group of 1. Compound 2 exhibits the reduced inhibitory activity against $NF-{\kappa}B$ activation and the others do not show the activity. Therefore ${\alpha},{\beta}-unsaturated$ carbonyl group of 1 should be important for its inhibitory activity.

Evaluation of Cytotoxicity to Rat Platelets by Menadione-Glutathione Conjugate and its Stability in Biological Assay System (Menadione의 대사체인 Menadione-Glutathione Conjugate(MEN-SG)가 흰쥐 혈소판에 미치는 세포독성의 평가 및 MEN-SG의 안정성에 관한 연구)

  • Seo, Dong-Chul;Chung, Sun-Hwa;Lee, Joo-Young;Kim, Mee-Jeong;Chung, Jin-Ho
    • Toxicological Research
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    • v.11 no.2
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    • pp.295-302
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    • 1995
  • Menadione-ghitathione conjugate (MEN-SG), a metabolite of menadione, is known to be a redoxcycler in rat hepatocyte subcellular fraction. Therefore, it was assumed that MEN-SG could exert cytotoxlclty to ral platelets, another target tissue of menadione. We first synthesized MEN-SG, the identity of which was verified by mass, $^1{H}$-NMR and UV-visible spectra. In addition, the stability of MEN-SG was investigated in biological assay system. MEN-SG was degraded in a time-dependent manner in DMSO which had been used as a vehicle and thus, tris-HCl buffer was used as a vehicle of MEN-SG despite the low solubility in it. Perchloric acid as well as platelets itself did not affect the stability of MEN-SG. Our next attempt was the evaluation of cytotoxicity of MEN-SG in rat platelets. MEN-SG did not induce cytotoxicity to rat platelets measured by two different methods, LDH release and turbidity changes. The extents of oxygen consumption by MEN-SG in intact platelets were significantly lower than those by menadione, though it had been observed that oxygen consumptions by menadione and MENSG were similar in subcellular fractioas of platelets. These results suggest that MEN-SG is not toxic to rat platelets despite its redox cycling capacity and glutathione conjugation reaction of menadione could be regarded as a detoxification process.

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Conjugate Gradient Least-Squares Algorithm for Three-Dimensional Magnetotelluric Inversion (3차원 MT 역산에서 CG 법의 효율적 적용)

  • Kim, Hee-Joon;Han, Nu-Ree;Choi, Ji-Hyang;Nam, Myung-Jin;Song, Yoon-Ho;Suh, Jung-Hee
    • Geophysics and Geophysical Exploration
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    • v.10 no.2
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    • pp.147-153
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    • 2007
  • The conjugate gradient (CG) method is one of the most efficient algorithms for solving a linear system of equations. In addition to being used as a linear equation solver, it can be applied to a least-squares problem. When the CG method is applied to large-scale three-dimensional inversion of magnetotelluric data, two approaches have been pursued; one is the linear CG inversion in which each step of the Gauss-Newton iteration is incompletely solved using a truncated CG technique, and the other is referred to as the nonlinear CG inversion in which CG is directly applied to the minimization of objective functional for a nonlinear inverse problem. In each procedure we only need to compute the effect of the sensitivity matrix or its transpose multiplying an arbitrary vector, significantly reducing the computational requirements needed to do large-scale inversion.

Generation of a Human Monoclonal Antibody to Cross-Reactive Material 197 (CRM197) and Development of a Sandwich ELISA for CRM197 Conjugate Vaccines

  • Kim, Dain;Yoon, Hyeseon;Kim, Sangkyu;Wi, Jimin;Chae, Heesu;Jo, Gyunghee;Yoon, Jun-Yeol;Kim, Heeyoun;Lee, Chankyu;Kim, Se-Ho;Hong, Hyo Jeong
    • Journal of Microbiology and Biotechnology
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    • v.28 no.12
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    • pp.2113-2120
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    • 2018
  • Cross-reactive material 197 ($CRM_{197}$) is a non-toxic mutant of diphtheria toxin containing a single amino acid substitution of glycine 52 with glutamic acid. $CRM_{197}$ has been used as a carrier protein for poorly immunogenic polysaccharide antigens to improve immune responses. In this study, to develop a sandwich ELISA that can detect $CRM_{197}$ and $CRM_{197}$ conjugate vaccines, we generated a human anti-$CRM_{197}$ monoclonal antibody (mAb) 3F9 using a phage-displayed human synthetic Fab library and produced mouse anti-$CRM_{197}$ polyclonal antibody. The affinity ($K_D$) of 3F9 for $CRM_{197}$ was 3.55 nM, based on Bio-Layer interferometry, and it bound specifically to the B fragment of $CRM_{197}$. The sandwich ELISA was carried out using 3F9 as a capture antibody and the mouse polyclonal antibody as a detection antibody. The detection limit of the sandwich ELISA was <1 ng/ml $CRM_{197}$. In addition, the 3F9 antibody bound to the $CRM_{197}$-polysaccharide conjugates tested in a dose-dependent manner. This ELISA system will be useful for the quantification and characterization of $CRM_{197}$ and $CRM_{197}$ conjugate vaccines. To our knowledge, this study is the first to generate a human monoclonal antibody against $CRM_{197}$ and to develop a sandwich ELISA for $CRM_{197}$ conjugate vaccines.