• Bulletin of the Korean Chemical Society
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• 제24권12호
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• pp.1742-1750
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• 2003

In order to characterize the hydrophobic parameters of N-acetyl amino acid amides in 1-octanol/water, a theoretical calculation was carried out using a solvation free energy density model. The hydrophobicity parameters of the molecules are obtained with the consideration of the solvation free energy over the solvent volume surrounding the solute, using a grid model. Our method can account for the solvent accessible surface area of the molecules according to conformational variations. Through a comparison of the hydrophobicity of our calculation and that of other experimental/theoretical works, the solvation free energy density model is proven to be a useful tool for the evaluation of the hydrophobicity of amino acids and peptides. In order to evaluate the solvation free energy density model as a method of calculating the activity of drugs using the hydrophobicity of its building blocks, the contracture of Bradykinin potentiating pentapeptide was also predicted from the hydrophobicity of each residue. The solvation free energy density model can be used to employ descriptors for the prediction of peptide activities in drug discovery, as well as to calculate the hydrophobicity of amino acids.

• 한국응용과학기술학회지
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• 제13권1호
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• pp.11-19
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• 1996

The liposomes have been developed in many drugs and cosmetics fields. The liposomes prepared with main compounds of the intercellular lipids and lecithin. Amphiphile nonionic surfactants used for (PEG) n-sitosterol(n=5), diethanolamine cetylphosphate. The effect of gelation for liposomes have been on swelling reaction which have been mixed phospholipid with polyol-group at the high temperature. There were very good encapsulated properties of the active ingredients whether hydrophilic-group(magnesium ascorbyl phosphate, allantoin, sodium hyaluronate) and hydrophobic-group(vitamin-E acetate, vitamin-A palmitate). Optimum condition of liposomes were passed five times in the microfluidizer(700bar), wetting reaction temperature was at $95{\pm}5^{\circ}C$ for a hours. Particle size distribution of the vesicles should be within range 50-560nm(mean 200nm). The stability of liposomes for the course of time was stabilized for six months at $45^{\circ}C$. Application of the cosmetic was prepared moisturizing cream with liposomes of the phospholipid base.

• Macromolecular Research
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• 제13권3호
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• pp.167-175
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• 2005

This review explores recent works involving the use of the self-assembled nanoparticles of bile acid-modified glycol chitosans (BGCs) as a new drug carrier for cancer therapy. BGC nanoparticles were produced by chemically grafting different bile acids through the use of l-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC). The precise control of the size, structure, and hydrophobicity of the various BGC nanoparticles could be achieved by grafting different amounts of bile acids. The BGC nanoparticles so produced formed nanoparticles ranging in size from 210 to 850 nm in phosphate-buffered saline (PBS, pH=7.4), which exhibited substantially lower critical aggregation concentrations (0.038-0.260 mg/mL) than those of other low-molecular-weight surfactants, indicating that they possess high thermodynamic stability. The SOC nanoparticles could encapsulate small molecular peptides and hydrophobic anticancer drugs with a high loading efficiency and release them in a sustained manner. This review also highlights the biodistribution of the BGC nanoparticles, in order to demonstrate their accumulation in the tumor tissue, by utilizing the enhanced permeability and retention (EPR) effect. The different approaches used to optimize the delivery of drugs to treat cancer are also described in the last section.

• 대한화장품학회지
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• 제49권2호
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• pp.97-106
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• 2023

본 연구에서는 사이클로덱스트린을 함유하여 고함량 세라마이드 제형 안정화 연구를 하고자 한다. 인체 피부 장벽인 세포간지질을 구성하는 세라마이드는 피부 속 수분을 보호하고 피부 장벽을 강화함으로써 보습유지에 매우 중요한 성분이다. 그러나 세라마이드는 난용성이므로 화장품 제형에 포함되었다 하더라도 서서히 겔화(gelation) 또는 결정화(crystallization)되어 경시적으로 석출되는 치명적인 문제점을 갖고 있어 고함량 처방하는 데 어려움이 있다. 사이클로덱스트린은 글루코오스 분자가 연결된 환형 올리고당으로 그 외부 표면은 친수성이고 내부는 소수성인 원통형 구조를 가지고 있어 난용성 약물의 용해성 개선 및 흡수성의 개선 등 약물의 물리화학적인 성질을 개선시키는 것으로 알려져 있다. 본 연구진은, 사이클로덱스트린을 활용하여 세라마이드 안정화 제형 실험 후 경도 측정 및 편광 현미경 관찰을 통해 세라마이드 석출 여부를 확인하였다. 본 연구 결과 사이클로덱스트린을 함유한 고함량 세라마이드 제형이 세라마이드의 겔화 또는 결정화를 예방하여 석출을 방지하는 효과가 있어 제형 안정성, 환경 조건별 보관 안정성 및 피부 보습력이 우수한 효과가 있다는 것을 확인하였다.

• Molecules and Cells
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• 제20권1호
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• pp.1-16
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• 2005

The peptidyl transferase center (PTC) is located in a protein free environment, thus confirming that the ribosome is a ribozyme. This arched void has dimensions suitable for accommodating the 3'ends of the A-and the P-site tRNAs, and is situated within a universal sizable symmetry-related region that connects all ribosomal functional centers involved in amino-acid polymerization. The linkage between the elaborate PTC architecture and the A-site tRNA position revealed that the A-to P-site passage of the tRNA 3'end is performed by a rotatory motion, which leads to stereochemistry suitable for peptide bond formation and for substrate mediated catalysis, thus suggesting that the PTC evolved by genefusion. Adjacent to the PTC is the entrance of the protein exit tunnel, shown to play active roles in sequence-specific gating of nascent chains and in responding to cellular signals. This tunnel also provides a site that may be exploited for local co-translational folding and seems to assist in nascent chain trafficking into the hydrophobic space formed by the first bacterial chaperone, the trigger factor. Many antibiotics target ribosomes. Although the ribosome is highly conserved, subtle sequence and/or conformational variations enable drug selectivity, thus facilitating clinical usage. Comparisons of high-resolution structures of complexes of antibiotics bound to ribosomes from eubacteria resembling pathogens, to an archaeon that shares properties with eukaryotes and to its mutant that allows antibiotics binding, demonstrated the unambiguous difference between mere binding and therapeutical effectiveness. The observed variability in antibiotics inhibitory modes, accompanied by the elucidation of the structural basis to antibiotics mechanism justifies expectations for structural based improved properties of existing compounds as well as for the development of novel drugs.

• 폴리머
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• 제34권6호
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• pp.547-552
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• 2010

생분해성 고분자는 제약 및 생명공학 분야에서 많은 관심을 받고 있는 물질로 특히 나노미립구의 형태로 약물전달체의 개발에 널리 이용되고 있다. 본 연구에서는 cyclohexanedimethanol과 oxalyl chloride를 pyridine의 존재 하에서 반응하여 고분자량의 생분해성 퍼옥살레이트 고분자를 합성하고 그 물리화학적 및 생물학적 특성을 조사하였다. 폴리옥살레이트는 분자량이 약 75000 Da 정도인 반결정성 고분자이며 물에서 가수분해가 일어남을 GPC와 NMR로 확인하였다. 소수성의 폴리옥살레이트는 단일유화법으로 나노미립구로 제조될 수 있으며 약물을 포접할 수 있고 아주 우수한 세포안정성을 가졌다. 용이한 합성과 우수한 물리화학적 및 생물학적 특성을 바탕으로 폴리옥살레이트 나노미립구는 약물전달체 개발에 아주 높은 잠재력이 있음을 확인하였다.

• 한국임상수의학회지
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• 제21권3호
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• pp.253-258
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• 2004

DNA double-strand break (DSB) is a serious treat for the cells including mutations, chromosome rearrangements, and even cell death if not repaired or misrepaired. Ku heterodimer regulatory DNA binding subunits (Ku70/Ku80) bound to double strand DNA breaks are able to interact with 470-kDa DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and the interaction is essential for DNA-dependent protein kinase (DNA-PK) activity. The Ku80 mutants were designed to bind Ku70 but not DNA end binding activity and the peptides were treated in breast cancer cells for co-therapy strategy to see whether the targeted inhibition of DNA-dependent protein kinase (DNA-PK) activity sensitized breast cancer cells to ionizing irradiation or chemotherapy drug to develop a treatment of breast tumors by targeting proteins involved in damage-signaling pathway and/or DNA repair. We designed domains of Ku80 mutants, 26 residues of amino acids (HN-26) as a control peptide or 38 (HNI-38) residues of amino acids which contain domains of the membrane-translocation hydrophobic signal sequence and the nuclear localization sequence, but HNI-38 has additional twelve residues of peptide inhibitor region. We observed that the synthesized peptide (HNI-38) prevented DNA-PKcs from binding to Ku70/Ku80, resulting in inactivation of DNA-PK complex activity in breast cancer cells (MDA-465 and MDA-468). Consequently, the peptide treated cells exhibited poor to no DNA repair, and became highly sensitive to irradiation or chemotherapy drugs. The growth of breast cancer cells was also inhibited. These results demonstrate the possibility of synthetic peptide to apply breast cancer therapy to induce apoptosis of cancer cells.

• Asian Pacific Journal of Cancer Prevention
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• 제16권9호
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• pp.3817-3825
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• 2015

Background: The human protein methyl-transferase DOT1L catalyzes the methylation of histone H3 on lysine 79 (H3K79) at homeobox genes and is also involved in a number of significant processes ranging from gene expression to DNA-damage response and cell cycle progression. Inhibition of DOT1L activity by shRNA or small-molecule inhibitors has been established to prevent proliferation of various MLL-rearranged leukemia cells in vitro, establishing DOT1L an attractive therapeutic target for mixed lineage leukemia (MLL). Most of the drugs currently in use for the MLL treatment are reported to have low efficacy, hence this study focused on various natural compounds which exhibit minimal toxic effects and high efficacy for the target receptor. Materials and Methods: Structures of human protein methyl-transferase DOT1L and natural compound databases were downloaded from various sources. Virtual screening, molecular docking, dynamics simulation and drug likeness studies were performed for those natural compounds to evaluate and analyze their anti-cancer activity. Results: The top five screened compounds possessing good binding affinity were identified as potential high affinity inhibitors against DOT1L's active site. The top ranking molecule amongst the screened ligands had a Glide g-score of -10.940 kcal/mol and Glide e-model score of -86.011 with 5 hydrogen bonds and 12 hydrophobic contacts. This ligand's behaviour also showed consistency during the simulation of protein-ligand complex for 20000 ps, which is indicative of its stability in the receptor pocket. Conclusions: The ligand obtained out of this screening study can be considered as a potential inhibitor for DOT1L and further can be treated as a lead for the drug designing pipeline.

• Asian Pacific Journal of Cancer Prevention
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• 제17권1호
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• pp.51-55
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• 2016

Phytochemical investigation of Pistacia integerrima has highlighted isolation of two known compounds naringenin (1) and dihydrokaempferol (2). A crude extract and these isolated compounds were here evaluated for their effects on reversion of multidrug resistance (MDR) mediated by P-glycoprotein (P-gp). The multidrug resistance P-glycoprotein is a target for chemotherapeutic drugs from cancer cells. In the present study rhodamine-123 exclusion screening test on human mdr1 gene transfected mouse gene transfected L5178 and L5178Y mouse T-cell lymphoma cells showed excellent MDR reversing effects in a dose dependent manner. In-silico molecular docking investigations demonstrated a common binding site for Rhodamine123, and compounds naringenin and dihydrokaempferol. Our results showed that the relative docking energies estimated by docking softwares were in satisfactory correlation with the experimental activities. Preliminary interaction profile of P-gp docked complexes were also analysed in order to understand the nature of binding modes of these compounds. Our computational investigation suggested that the compounds interactions with the hydrophobic pocket of P-gp are mainly related to the inhibitory activity. Moreover this study s a platform for the discovery of novel natural compounds from herbal origin, as inhibitor molecules against the P-glycoprotein for the treatment of cancer.

• Journal of Pharmaceutical Investigation
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• 제40권2호
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• pp.73-78
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• 2010

Hydrogels are thought to be a promising delivery carrier for protein drugs because of their favorable aqueous environment compared with nano/micro-particles of hydrophobic polymer such as PLGA. In this study, nano-sized hydrogels (nanogels) were fabricated using inverse-miniemulsion polymerization method. The mean size of nanogels in range of 90-160nm and affected by the preparation parameters such as sonication time and concentration of monomer. While longer sonication time and lower concentration of acrylamide monomer showed a tendency to produce smaller nanogels and to have lower lysozyme activity, variation of bis-methylene acrylamide concentration made no difference. Although both longer soncaton time and lower acrylamide concentration increased in vitro release rate, acrylamide concentration was more effectively affected to the control of protein release rate, which indicated that the release rate of protein from nanogels affected by not only their size but also internal structure. In conclusion, nanogels prepared by inverse-miniemulsion can be a useful carrier for application of protein drug, because of simple process, minimum contact of organic solvent and high protein activity.