• Bulletin of the Korean Chemical Society
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• 제27권5호
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• pp.613-630
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• 2006

Nucleic acids are virtually omnipresent; they exist in every living being. These macromolecules constitute the most important genetic storage material: the genes. Genes are conserved throughout the evolution of all living beings; they are transmitted from the parents to their offspring. Many interdisciplinary research groups are interested in modifying nucleic acids for use in a wider variety of applications. These modified oligonucleotides are used in many diverse fields, including diagnostics, detection, and therapeutics. In this account, we summarize our research efforts related to modified nucleic acid systems. First, we discuss our syntheses of modified oligonucleotides containing fluorescent tags for use as molecular probes (molecular beacons) to detect single-nucleotide polymorphisim (SNP) in nucleic acids and to distinguish between the B and Z forms of DNA. We also describe our research efforts into oligonucleotides functionalized with steroid derivatives to enhance their cell permeability, and the synthesis of several calix[4]arene-oligonucleotide conjugates possessing the ability to form defined triplexes. In addition, we have performed systematic studies to have an understanding about the functional groups necessary for a given nucleoside to behave as an organo or hydrogelator. The aggregation properties of a number of nucleoside-based phospholipids have been examined in different solvents; some of these derivatives are potential candidates for use as nucleoside-based liposomes. Finally, we also describe our research efforts toward the preparation of isoxazole- and isoxazoline-containing nucleoside derivatives and the determination of their antiviral activities.

• BMB Reports
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• 제43권4호
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• pp.250-256
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• 2010

Natural phosphodiester bond CpG-DNA that contains immunomodulatory CpG motifs (PO-DNA) upregulates the expression of proinflammatory cytokines and induces an Ag-driven Th1 response in a CG sequence-dependent manner in mice. In humans, only phosphorothioate backbone-modified CpG-DNA (PS-DNA) and not PO-DNA has immunomodulatory activity. In this study, we found that liposome-encapsulated PO-DNA upregulated the expression of human $\beta$-defensin-2 (hBD-2) and major histocompatibility class II molecules (HLA-DRA) in a CG sequence-dependent and liposome- dependent manner in human B cells. Of the three different liposomes, DOTAP has the unique ability to enhance the immunomodulatory activity of PO-DNA. In contrast, HLA-DRA and hBD-2 promoter activation can be induced by liposome-encapsulated PS-DNA in a CG sequence-independent manner, depending on the CpG-DNA species. Our observations demonstrate that, when encapsulated with a proper liposome in the immune system, natural PO-DNA has the potential to be a useful therapy for the regulation of the innate immune response.

• 대한수의학회지
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• 제32권2호
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• pp.251-258
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• 1992

Stable plurilamellar vesicle(SPLV) 제작법을 이용한 liposomal cephalexin으로 젖소의 Staphylococcus aureus성 유방염에 대해 건유기 치료를 시도하였다. SPLV의 모양과 크기를 transmission electron microscopy로 관찰하였으며 SPLV의 포획율 및 안정성은 high performance liquid chromatography 및 liquid scintillation counting으로 조사한 바 SPLV의 크기는 대개 직경 $0.1{\sim}4.0{\mu}m$였고, cephalexin 포획율은 $25.8{\pm}3.1$ $(mean{\pm}SE)$였으며 $4^{\circ}C$ 보관시 0, 24, 48, 72 및 96 시간후의 유리농도백분율은 각각 1.1, 3.9, 6.5, 7.5 및 8.4%였다. S aureus에 감염된 45분방에 대하여 15분방씩 3군으로 나누어 각 분방당 250mg의 liposomal cephalexin(LC군), 250mg free cephalexin(FC)군 및 blank liposome을 첨가한 250mg cephalexin(BLC)군을 건유시 분방내 주입한 후 분만당일에 균분리 및 동정을 실시한 바 LC군, FC군 및 BLC군에서 각각 1, 8 및 7분방에서 상기와 동일한 균이 분리되어 LC군이 타군에 비해 유의한 치료효과를 나타내었다.

• BMB Reports
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• 제39권3호
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• pp.270-277
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• 2006

Helices 4 and 5 of the Bacillus thuringiensis Cry4Ba $\delta$-endotoxin have been shown to be important determinants for mosquito-larvicidal activity, likely being involved in membrane-pore formation. In this study, the Cry4Ba mutant protein containing an additional engineered tryptic cleavage site was used to produce the $\alpha4$-$\alpha5$ hairpin peptide by an efficient alternative strategy. Upon solubilization of toxin inclusions expressed in Escherichia coli and subsequent digestion with trypsin, the 130-kDa mutant protoxin was processed to protease-resistant fragments of ca. 47, 10 and 7 kDa. The 7-kDa fragment was identified as the $\alpha4$-loop-$\alpha5$ hairpin via N-terminal sequencing and mass spectrometry, and was successfully purified by size-exclusion FPLC and reversed-phase HPLC. Using circular dichroism spectroscopy, the 7-kDa peptide was found to exist predominantly as an $\alpha$-helical structure. Membrane perturbation studies by using fluorimetric calcein-release assays revealed that the 7-kDa helical hairpin is highly active against unilamellar liposomes compared with the 65-kDa activated full-length toxin. These results directly support the role of the $\alpha4$-loop-$\alpha5$ hairpin in membrane perturbation and pore formation of the full-length Cry4Ba toxin.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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• pp.278-278
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• 1996

Judging from hydrocortisone concentration in dosing area, the extent of absorption was reduced in the liposome-gel formulation. However, higher and sustained skin concentrations of hydrocortisone were achieved for the liposome-gel as compared to the ointment. Drug concentration in both viable and deep skin reached its maximum within 0.5 h after application of both formulations to both skin types. Drug concentrations in both skins from the ointment declined with time, while those from the liposome-gel were greatly sustained. The sustainment by the liposome-gel was more remarkable in the viable skin than in the deep skin. Drug concentration in the viable skin could be maintained at a nearly constant level for over 8 h by applying the liposome-gel. As a result, a 5-fold higher viable skin drug concentration was obtained from the liposome-gel than from the ointment at 8 h after the application to the SC-removed skin. However, the plasma concentration of hydrocortisone at 4 h from the liposome-gel was only one-fourth (p<0.01) the value from the ointment when the drug was applied to the SC-removed skin, consistent with. the lower urinary (one-third, p<0.05) and fecal (one-half, p＜0.05) excretion. Conclusions : Retarded diffusion of the drug from the skin to the systemic blood stream appears to be a potential factor in the sustained skin concentration of hydrocortisone from the liposome-gel, Interaction of hydrocortisone in the skin with phosphatidylcholine, a component of the liposomes and skin, may well be a factor in retarding the diffusion of the drug in the skin.

• Applied Biological Chemistry
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• 제42권3호
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• pp.205-209
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• 1999

리포솜을 구성하는 지질 내의 콜레스테롤 함량이 포집된 ascorbic acid의 안정성에 미치는 영향을 조사하였다. 리포솜 내에서의 콜레스테롤 함량이 증가할수록 탈수화/재수화법으로 제조된 리포솜의 크기는 증가하였으며, 가해진 ascorbic acid의 안정성은 증대되었으며, 외부의 pH 영향을 크게 받지 않았다. 그러나, $4^{\circ}C$에서 저장한 경우에 비하여 $37^{\circ}C$에서 저장한 경우에는 포집된 ascorbic acid의 산화가 빨리 진행되었다. 이러한 결과는 리포솜의 콜레스테롤 함량이 포집된 ascorbic acid의 안정성에 영향을 미침을 의미한다.

• Journal of Dairy Science and Biotechnology
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• 제24권1호
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• pp.53-63
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• 2006

Nano and micro capsulation (NM capsulation) involve the incorporation for nanofood materials, enzymes, cells or other materials in small capsules. Since Kim D. M. (2001) showed that a new type of food called firstly the name of nanofood, which means nanotechnology for food, and the encapsulated materials can be protected from moisture, heat or other extreme conditions, thus enhancing their stability and maintaining viability applications for this nanofood technique have increased in the food. NM capsules for nanofood is also utilized to mask odours or tastes. Various techniques are employed to form the capsules, including spray drying, spray chilling or spray cooling, extrusion coating, fluidized bed coating, liposome entrapment, coacervation, inclusion complexation, centrifugal extrusion and rotational suspension separation. Each of these techniques is discussed in this review. A wide variety of nanofood is NM capsulated - flavouring agents, acids, bases, artificial sweeteners, colourants, preservatives, leavening agents, antioxidants, agents with undesirable flavours, odours and nutrients, among others. The use of NM capsulation for sweeteners such as aspartame and flavors in chewing gum is well known. Fats, starches, dextrins, alginates, protein and lipid materials can be employed as encapsulating materials. Various methods exist to release the ingredients from the capsules. Release can be site-specific, stage-specific or signaled by changes in pH, temperature, irradiation or osmotic shock. NM capsulation for the nanofood, the most common method is by solvent-activated release. The addition of water to dry beverages or cake mixes is an example. Liposomes have been applied in cheese-making, and its use in the preparation of nanofood emulsions such as spreads, margarine and mayonnaise is a developing area. Most recent developments include the NM capsulation for nanofood in the areas of controlled release, carrier materials, preparation methods and sweetener immobilization. New markets are being developed and current research is underway to reduce the high production costs and lack of food-grade materials.

• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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• pp.2837-2840
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• 2012

We investigated whether IFN-${\beta}$ inhibits the growth of human malignant glioma and induces glioma cell apoptosis using the human IFN-${\beta}$ gene transfected into glioma cells. A eukaryonic expression vector ($pSV2IFN{\beta}$) for IFN-${\beta}$ was transfected into the glioma cell line SHG44 using liposome transfection. Stable transfection and IFN-${\beta}$ expression were confirmed using an enzyme-linked immunosorbent assay (ELISA). Cell apoptosis was also assessed by Hoechst staining and electron microscopy. In vivo experiments were used to establish a SHG44 glioma model in nude mice. Liposomes containing the human IFN-${\beta}$ gene were injected into the SHG44 glioma of nude mice to observe glioma growth and calculate tumor size. Fas expression was evaluated using immunohistochemistry. The IFN-${\beta}$ gene was successfully transfected and expressed in the SHG44 glioma cells in vitro. A significant difference in the number of apoptotic cells was observed between transfected and non-transfected cells. Glioma growth in nude mice was inhibited in vivo, with significant induction of apoptosis. Fas expression was also elevated. The IFN-${\beta}$ gene induces apoptosis in glioma cells, possibly through upregulation of Fas. The IFN-${\beta}$ gene modulation in the Fas pathway and apoptosis in glioma cells may be important for the treatment of gliomas.

• Journal of Microbiology and Biotechnology
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• 제21권8호
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• pp.802-807
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• 2011

Cationic liposomes have been actively used as gene delivery vehicle because of their minimal toxicity, but their relatively low efficiency of gene delivery is the major disadvantage of these vectors. Recently, cysteine residue incorporation to HIV-1 Tat peptide increased liposomemediated transfection compared with unmodified Tat peptide. Therefore, we designed a novel modified Tat peptide having a homodimeric (Tat-CTHD, Tat-NTHD) and closed structure (cyclic Tat) simply by using the disulfide bond between cysteines to develop a more efficient and safe nonviral gene delivery system. The mixing of Tat-CTHD and Tat-NTHD with DNA before mixing with lipofectamine increased the transfection efficiency compared with unmodified Tat peptide and lipofectamine only in MCF-7 breast cancer cells and rat vascular smooth muscle cells. However, cyclic Tat did not show any improvement in the transfection efficiency. In the gel retardation assay, Tat-CTHD and Tat-NTHD showed more strong binding with DNA than unmodified Tat and cyclic Tat peptide. This enhancement was only shown when Tat-CTHD and Tat-NTHD were mixed with DNA before mixing with lipofectamine. The effects of Tat- CTHD and Tat-NTHD were also valid in the experiment using DOTAP and DMRIE instead of lipofectamine. We could not find any significant cytotoxicity in the working concentration and more usage of these peptides. In conclusion, we have designed a novel transfection-enhancing peptide by easy homodimerization of Tat peptide, and the simple mix of these novel peptides with DNA increased the gene transfer of cationic lipids more efficiently with no additional cytotoxicity.

• 한국정보통신학회논문지
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• 제20권12호
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• pp.2395-2400
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• 2016

암 환자들을 대상으로 하는 항암치료법은 나노입자, 폴리머 중합체, 지질, 리포솜 등을 치료 전달체로 이용하여 항암치료를 진행하는 방법들이 주로 활발하게 사용되고 있다. 이러한 전달체는 항암 치료제를 직접 암세포로 정확하게 표적 운반하는 정확성, 정확하게 운반한 후 선택적으로 항암치료제를 방출해야하는 유출제어, 다른 일반 세포들을 약물로부터 보호하는 기능 등을 동시에 가지고 있어야 하지만, 대부분 항암약물의 독성에 기인한 부작용이 발생하고 있다. 겸형적혈구는 암세포주변 혈관세포와 멤브레인 표면에 존재하는 리셉터 사이에의 점착성이 존재하며 추가적 생화학처리 없이 암세포 주변에 표적화가 가능함을 보인다. 또한, 암세포 주변의 혈관의 구조적 변화특성은 겸형적혈구의 중합화 반응을 증가시킨다. 따라서 본 논문에서는 겸형적혈구를 이용한 새로운 항암치료법의 효과를 정량적 혈관분석 방법을 통해 제시하고자 한다.