• Title/Summary/Keyword: Chemical Modification

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THE EFFECT OF GENETIC VARIATION IN THE DNA BASE REPAIR GENES ON THE RISK OF HEAD AND NECK CANCER (DNA 염기손상 치유유전자의 변이와 두경부암 발생 위험성)

  • Oh, Jung-Hwan;Yoon, Byung-Wook;Choi, Byung-Jun
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.34 no.5
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    • pp.509-517
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    • 2008
  • DNA damage accumulates in cells as a result of exposure to exogenous agents such as benzopyrene, cigarette smoke, ultraviolet light, X-ray, and endogenous chemicals including reactive oxygen species produced from normal metabolic byproducts. DNA damage can also occur during aberrant DNA processing reactions such as DNA replication, recombination, and repair. The major of DNA damage affects the primary structure of the double helix; that is, the bases are chemically modified. These modification can disrupt the molecules'regular helical structure by introducing non-native chemical bonds or bulky adducts that do not fit in the standard double helix. DNA repair genes and proteins scan the global genome to detect and remove DNA damage and damage to single nucleotides. Direct reversal of DNA damage, base excision repair, double strand break. DNA repair are known relevant DNA repair mechanisms. Four different mechanisms are distinguished within excision repair: direct reversal, base excision repair, nucleotide excision repair, and mismatch repair. Genetic variation in DNA repair genes can modulate DNA repair capacity and alter cancer risk. The instability of a cell to properly regulate its proliferation in the presence of DNA damage increase risk of gene mutation and carcinogenesis. This article aimed to review mechanism of excision repair and to understand the relationship between genetic variation of excision repair genes and head and neck cancer.

Genenation of structural diversity in polyketides by combinatorial biosynthesis of polyketides: Part I. Generation of multiple bioactive macrolides by hybrid modular polyketide synthases in Streptomyces venezuelae, Part II. Production of novel rifamycins by combinatorial biosynthesis

  • Yoon, Yeo-Joon
    • Proceedings of the Korean Society for Applied Microbiology Conference
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    • 2002.10a
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    • pp.18-25
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    • 2002
  • The pikromycin biosynthetic system in Streptomyces venezuleae is unique for its ability to produce two groups of antibiotics that include the 12-membered ring macrolides methymycin and neomethymycin, and the 14-membered ring macrolides narbomycin and pikromycin. The metabolic pathway also contains two post polyketide-modification enzymes, a glycosyltransferase and P450 hydroxylase that have unusually broad substrate specificities. In order to explore further the substrate flexibility of these enzymes a series of hybrid polyketide synthases were constructed and their metabolic products characterized. The plasmid-based replacement of the multifunctional protein subunits of the pikromycin PKS in S. venezuelae by the corresponding subunits from heterologous modular PKSs resulted in recombinant strains that produce both 12- and 14-membered ring macrolactones with predicted structural alterations. In all cases, novel macrolactones were produced and further modified by the DesVII glycosyltransferase and PikC hydroxylase leading to biologically active macrolide structures. These results demonstrate that hybrid PKSs in S. venezuelae can produce a multiplicity of new macrolactones that are modified further by the highly flexible DesVII glycosyltransferase and PikC hydroxylase tailoring enzymes. This work demonstrates the unique capacity of the S. venezuelae pikromycin pathway to expand the toolbox of combinatorial biosynthesis and to accelerate the creation of novel biologically active natural products. The polyketide backbone of rifamycin B is assembled through successive condensation and ${\beta}$-carbonyl processing of the extender units by the modular rifamycin PKS. The eighth module, in the RifD protein, contains nonfunctional DH domain and functional KR domain, which specify the reduction of the ${\beta}$-carbonyl group resulting in the C-21 bydroxyl of rifamycin B. A four amino acid substitution and one amino acid deletion were introduced in the putative NADPH binding motif in the proposed KR domain encoded by rifD. This strategy of mutation was based on the amino acid sequences of the corresponding motif of the KR domain of module 3 in the RifA protein, which is believed dysfunctional, so as to introduce a minimum alteration and retain the reading frame intact, yet ensure loss of function. The resulting strain produces linear polyketides, from tetraketide to octaketide, which are also produced by a rifD disrupted mutant as a consequence of premature termination of polyketide assembly. Much of the structural diversity within the polyketide superfamily of natural products is due to the ability of PKSs to vary the reduction level of every other alternate carbon atom in the backbone. Thus, the ability to introduce heterologous reductive segments such as ketoreductase (KR), dehydratase (DH), and enoylreductase (ER) into modules that naturally lack these activities would increase the power of the combinatorial biosynthetic toolbox. The dehydratase domain of module 7 of the rifamycin PKS, which is predicted to be nonfunctional in view of the sequence of the apparent active site, was replaced with its functional homolog from module 7 of rapamycin-producing polyketide synthase. The resulting mutant strain behaved like a rifC disrupted mutant, i.e., it accumulated the heptaketide intermediate and its precursors. This result points out a major difficulty we have encountered with all the Amycolatopsis mediterranei strain containing hybrid polyketide synthases: all the engineered strains prepared so far accumulate a plethora of products derived from the polyketide chain assembly intermediates as major products instead of just analogs of rifamycin B or its ansamycin precursors.

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Antioxidative Effects of Water-Soluble Chitinous Compounds on Oxidation of Low Density Lipoprotein in Macrophages (대식세포에서 지단백 산화에 대한 수용성 Chitinous Compounds의 항산화 효과에 대한 연구)

  • 이세희;박성희;이용진;윤정한;최연정;최정숙;강영희
    • Journal of Nutrition and Health
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    • v.36 no.9
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    • pp.908-917
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    • 2003
  • It has been proposed that oxidative modification of LDL (oxLDL) plays a significant role in the pathogenicity of atherogenesis. We tested the hypothesis that chitin and chitosan may function as antioxidants with respect to 0.1 mg cholesterol/ml LDL incubated with 5 $\mu$ M Cu$^2$$^{+}$alone or in the P338Dl mouse macrophage system using L-ascorbic acid as a standard classical antioxidant. The degree of oxLDL formation was ascertained by the relative electrophoretic mobility (rEM) in the combination of thiobarbituric acid reactive substances (TBARS) levels, and the cytotoxicity of oxLDL was detected by macrophage viability. The oxLDL uptake and foam cell formation of macrophages were measured by Oil Red O staining. Incubation with Cu$^2$$^{+}$and macrophages increased rEM of LDL and stimulated TBARS formation. Culture of macrophages with LDL in the presence 5 $\mu$ M Cu$^2$$^{+}$induced macrophage death. In cell-free system 200 $\mu$g/ml water-soluble chitosan and chitosan-oligosaccharide blocked oxLDL formation. Water-soluble chitosan and chitosan-oligosaccharide blocked oxLDL formation near-completely relative to L-ascorbic acid, whereas water-soluble chitin and chitin-oligosaccharide had no measurable antioxidant effect. In macrophage system water-soluble chitosan and chitosan-oligosaccharide blocked oxidation of LDL with a significant increase in cell viability, and decreased TBARS in medium. As for the inhibitory effect on macrophage foam cell formation, chitosan and its oligosaccharide, but not watersoluble chitin, revealed the effectiveness. The endothelial expression of lectin-like oxLDL receptor-1 (LOX-1) was tested by Western blot analysis, and chitosan, chitosan-oligosaccharide and chitin-oligosaccharide blocked LOX-1 expression. These results indicate that water-soluble chitosan and its oligosaccharide showed the inhibitory effect on Cu$^2$$^{+}$-induced LDL oxidation of macrophages, and chitosan, chitosan-oligosaccharide and chitin-oligosaccharide had blocking effect on oxLDL receptor expression in the human umbilical vein endothelial system. Thus, water-soluble chitosan and its oligosaccharides possess anti-atherogenic potentials possibly through the inhibition of macrophage LDL oxidation or endothelial oxLDL receptor expression depending on chemical types.l types.

The Effect of Vitamin A Derivatives on the Activity of Drug-metabolizing Enzyme in Rat Liver (Vitamin A 유도체로 인한 간의 약물대사효소 변동)

  • Lee, H.W.;Ryu, K.Z.;Ro, J.Y.;Hong, S.S.
    • The Korean Journal of Pharmacology
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    • v.18 no.1
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    • pp.65-72
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    • 1982
  • It has been known that retinoids are intrinsically of critical importance for control of premalignant epithelial cell differentiation. In the absence of retinoids, normal cellular differentiation and growth does not occur in epithelia such as those of trachea and bronchi. Furthermore, it was also reported that retinoid deficiency enhanced susceptibility to chemical carcinogenesis in the respiratory system, in the bladder, and in the colon of the experimental animal. In 1974, Bollag examined the effects of synthetic retinoids in prevention of development of cancer and demonstrated synthetic retinoids to have more favorable therapeutic index than retinoic acid for causing regression of skin papilloma in mice. Therefore, it was assumed that this anticarcinogenic effect of vitamin A derivatives could be due to modification of the metabolism of the carcinogenic polycyclic hydrocarbon, which must first be activated to exert their effect. Hill and Shih reported that vitamin A compounds and analogs had inhibitory effect on drug metabolizing enzyme from liver and lung tissue of mouse and hamster. Lucy suggested that the chemoprevention effect of vitamin A derivatives is due to reaction with molecular oxygen, and it is possible that inhibition of hydroxybenzpyrene formation is a result of this property. On the other hand, butylated hydroxytoluene which is a potent antioxidant strongly inhibited the formation of mammary tumor induced by dimethylbenranthracene. Also, it was observed that this antioxidant inhibited cancer induction in rats by N-2-fluo-renylacetamide. The purpose of this experiment was to investigate the effect of vitamin A derivatives such as retinoic acid and retinoid on drug-metabolizing enzyme and to determine whether riboflavin tetrabutylate or vitamin E could prevent of modify any changes induced by vitamin A delivatives in the rats. The results obtained were as followings. 1) Body weight was significantly reduced by retinoic acid, but not by retinoid. 2) Retinoic acid markedly increased liver weight while retincid showed no effect on liver weight. Treatment of riboflavin tetrabutylate did not affect retinoic acid-induced change in both body weight and liver weight. 3) Both retinoic acid and retinoid remarkably decreased the activity of aminopyrine demethylase. Pretreatment of riboflavin tetrabutylate, however, prevented inhibitory effect of retinoic acid on the enzyme activity. 4) No significant effect of vitamin E on aminopyrine demethylase was observed in both groups treated with retinoic acid and retinoid.

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A Study on Influence of Firing Temperature and Temper Content on the Physical Properties of Earthenware Coffin (소성온도와 혼입물 함량이 옹관의 물성에 주는 영향에 관한 연구)

  • Kim, Kyu Been;Chung, Kwang Yong
    • Journal of Conservation Science
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    • v.30 no.4
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    • pp.373-381
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    • 2014
  • Adding temper into clay prevents to shrink and crack, or twist the clay during the dry process. The purpose of this study is to identify the role of temper and the physical property of earthenware coffin according to the clay state modification in the reduction firing based on earthenware coffins found in Naju which had been made in Three Kingdom Period. Clay from the Oryang-dong site in Naju was used as circle shaped samples. The samples were tempered with various proportions (0%, 20%, 40%) and fired in various temperature ($1000^{\circ}C$, $1100^{\circ}C$, $1200^{\circ}C$). Physical properties were identified by macroscopy, an optical microscope (x50), specific gravity and porosity. Chemical components and existence of specific minerals were identified by analysing XRF and XRD. As a result, the more firing temperature increase, clay volume expansion. To prevent the volume expansion, temper was added.

Synthesis and Small Animal Brain PET Study of a Serotonin Receptor Radiotracer, 18F-Mefway (세로토닌 5-HT1A수용체 방사성 추적자 18F-Mefway의 합성과 소동물 뇌 PET 연구)

  • Ahn, Sung-Min;Hong, Tae-Kee;Ryu, Young-Hoon;Choi, Jae-Yong;Kim, Sung-Chul
    • The Journal of the Korea Contents Association
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    • v.9 no.11
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    • pp.262-270
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    • 2009
  • $^{18}F$-mefway has been developed as radioligand for serotonin receptor 5-$HT_{1A}$. The object of this study was to obtain the mefway precursor with the higher yield than previous method and to identify whether $^{18}F$-mefway can bind to 5-$HT_{1A}$ or not. from microPET imaging of small animal brain. Precursor was prepared by a modification of the reported procedure then [$^{18}F$] labeling was performed by adding $^{18}F$ ion at $130^{\circ}C$ in the hot cell for 30min. After purification of reaction mixture using alumina Sep-pak and HPLC, microPET images of small animal brain were determined. The chemical yield of precursor was increased from 9% to 34% using oxalyl chloride and LAH/diethylether. We synthesized a precursor which was successfully labeled with no-carrier-added $^{18}F$-by new synthetic route. This research suggest that $^{18}F$-mefway will be used a radiopharmaceutical for evaluation of central nerve system disorder as imaging a gent for 5-$HT_{1A}$ receptor.

Effect of Fluorination and Ultrasonic Washing Treatment on Surface Characteristic of Poly(ethylene terephthalate) (불소화 및 초음파 수세가 폴리(에틸렌 테레프탈레이트) 필름의 표면 특성에 미치는 영향)

  • Kim, Do Young;In, Se Jin;Lee, Young-Seak
    • Polymer(Korea)
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    • v.37 no.3
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    • pp.316-322
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    • 2013
  • In this study, poly(ethylene terephthalate) (PET) was treated with fluorination and ultrasonic washing treatment for hydrophilic modification of PET film. We measured the change of surface modified PET film surface characteristics using contact angle, surface free energy, FE-SEM, AFM and XPS. After direct fluorination and ultrasonic washing treatment, the water contact angle was measured to be $10.81^{\circ}$, 85% reduction compared to the untreated PET film. Total surface free energy has been measured to be $42.25mNm^{-1}$, 650% increase compared to the untreated PET film. Also RMS roughness has been measured to be 1.965 nm, 348% increase compared to the untreated PET film. Hydrophilic functional group C-OH bond concentration has increased approximately 3 times. These results are attributed to the hydrophilic functional group and cavitation due to chemical etching. From this result, it was suggested that the fluorination-ultrasonic washing treatment method could be useful to make PET film surface hydrophilic.

Improvement of the Adhesion Properties between Aluminum and a Parylene-C Film by Using the Duoplasmatron Ion Source (Duoplasmatron Ion Source를 이용한 Parylene과 Al의 접착력 향상에 관한 연구)

  • Choi, Sung-Chang
    • Journal of the Korean Vacuum Society
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    • v.21 no.2
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    • pp.78-85
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    • 2012
  • In order to improve the adhesion between poly-monochloro-para-xylylene (Parylene-C) film and Aluminum thin film, the surface of Parylene-C film was irradiated by ${O_2}^+$ and $Ar^+$ ion beam generated by duoplamatron ion source. The ion dose of $Ar^+$ and ${O_2}^+$ was changed from $5{\times}10^{14}$ to $1{\times}10^{17}/cm^2$ and the ion beam energy was 1 kV. Contact angles of water on Parylene-C modified by $Ar^+$ and ${O_2}^+$ ion irradiation decreased from $78^{\circ}$ to around $17^{\circ}$, and $9^{\circ}$, respectively. X-ray photoelectron spectroscopy analysis shows that the hydrophilic groups were formed on the surface of Parylene-C by chemical reaction between the unstable chains induced by the ion irradiation and oxygen ions or residual oxygen gas. The hydrophilic groups were identified as C-O bond, C=O bond and (C=O)-O bond. The cross cut tape test which was applied to characterize the adhesion between Al thin film and Parylene-C film modified by ${O_2}^+$ ions irradiation shows that the adhesion strength was improved as increasing ion dose.

A Study on the H3PO4-Treated Soft Carbon as Anode Materials for Lithium Ion Batteries (리튬이온전지용 소프트카본 음극 소재의 인산 처리에 대한 연구)

  • Jo, Yong-Nam;Lee, En-Young;Park, Min-Sik;Hong, Ki-Joo;Lee, Sang-Ick;Jeong, Hu-Young;Lee, Zonghoon;Oh, Seung M.;Kim, Young-Jun
    • Journal of the Korean Electrochemical Society
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    • v.15 no.4
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    • pp.207-215
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    • 2012
  • Soft carbons are prepared by heat-treatment of cokes with different amounts of phosphoric acid (2, 4.5, and 10 wt% vs. cokes) at $900^{\circ}C$ to be used as anode materials for lithium ion batteries. From electrochemical measurements combined with structural analyses, we confirm that abundant nano-pores are existed in the microstructure of soft carbons prepared with the phosphoric acid, which are responsible for further lithium ion storage. Significant increase in reversible capacity of soft carbon is attained in proportion to added amount of the phosphoric acid. We also demonstrate the effect of structural modification with phosphoric acid on electrochemical performance of soft carbon to elucidate the origin of additional capacity.

Mesoporous Silica Catalysts Modified with Sulfonic Acid and Their Catalytic Activity on Ring Opening Polymerization of Octamethylcyclotetrasiloxane (술폰산으로 표면개질된 메조기공 실리카 촉매의 제조 및 Octamethylcyclotetrasiloxane 개환중합에서의 촉매 활성)

  • Lee, Yeonsong;Hwang, Ha Soo;Lee, Jiyoung;Lo, Nu Hoang Tien;Nguyen, Tien Giang;Lee, Donghyun;Park, In
    • Applied Chemistry for Engineering
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    • v.31 no.4
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    • pp.383-389
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    • 2020
  • Mesoporous silica solid catalysts modified with sulfonic acid were prepared for cationic ring-opening polymerization of octamethylcyclotetrasiloxane (D4). Two sets of MCM-41 (1.7 and 2.8 nm) and SBA-15 (8.1 and 15.9 nm) with different pore sizes were used as catalyst supports. The surface of silica materials was modified with (3-mercaptopropyl)trimethoxysilane by silylation reaction and oxidized to sulfonic acid. The structures of the prepared catalysts were examined by X-ray diffraction and nitrogen adsorption-desorption. The pore size, specific surface area, and pore volume of the modified solid catalysts decreased slightly. In addition, the modification of the sulfonic acid on the silica surface was confirmed by using infrared spectroscopy and nuclear magnetic resonance spectroscopy. To observe the effect of the particle size on the catalytic activity, it was observed with a scanning electron microscope. The catalysts were used to synthesize PDMS through a ring-opening polymerization of D4, and the conversion and polymerization rate of the polymerization reaction depended on the pore size, specific surface area, particle size, and particle agglomeration of the catalysts. In order for the polymerization rate, the catalyst prepared with SBA-15 of 8.1 nm pore size had the fastest reaction rate and showed the best catalytic activity.