• Molecules and Cells
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• v.39 no.2
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• pp.156-162
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• 2016

Estrogen receptor ${\alpha}$ (ER-${\alpha}$), which is involved in bone metabolism and breast cancer, has been shown to have transcriptional targets. Dlx3 is essential for the skeletal development and plays an important role in osteoblast differentiation. Various osteogenic stimulators and transcription factors can induce the protein expression of Dlx3. However, the regulatory function of ER-${\alpha}$ in the Dlx3 mediated osteogenic process remains unknown. Therefore, we investigated the regulation of Dlx3 and found that ER-${\alpha}$ is a positive regulator of Dlx3 transcription in BMP2-induced osteoblast differentiation. We also found that ER-${\alpha}$ interacts with Dlx3 and increases its transcriptional activity and DNA binding affinity. Furthermore, we demonstrated that the regulation of Dlx3 activity by ER-${\alpha}$ is independent of the ligand (estradiol) binding domain. These results indicate that Dlx3 is a novel target of ER-${\alpha}$, and that ER-${\alpha}$ regulates the osteoblast differentiation through modulation of Dlx3 expression and/or interaction with Dlx3.

• Journal of Pharmacopuncture
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• v.19 no.1
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• pp.37-44
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• 2016

Objectives: This study examined the relative efficacies of a derivative of betulinic acid (dBA) and its poly (lactide-co-glycolide) (PLGA) nano-encapsulated form in A549 lung cancer cells in vivo and in co-mutagen [sodium arsenite (SA) + benzo[a]pyrene (BaP)]-induced lung cancer in mice in vivo. Methods: dBA was loaded with PLGA nanoparticles by using the standard solvent displacement method. The sizes and morphologies of nano-dBA (NdBA) were determined by using transmission electron microscopy (TEM), and their intracellular localization was verified by using confocal microscopy. The binding and interaction of NdBA with calf thymus deoxyribonucleic acid (CT-DNA) as a target were analyzed by using conventional circular dichroism (CD) and melting temperature (Tm) profile data. Apoptotic signalling cascades in vitro and in vivo were studied by using an enzyme-linked immunosorbent assay (ELISA); the ability of NdBA to cross the blood-brain barrier (BBB) was also examined. The stage of cell cycle arrest was confirmed by using a fluorescence-activated cell-sorting (FACS) data analysis. Results: The average size of the nanoparticles was ~ 110 nm. Confocal microscopy images confirmed the presence of NdBA in the cellular cytoplasm. The bio-physical properties of dBA and NdBA ascertained from the CD and the Tm profiles revealed that NdBA had greater interaction with the target DNA than dBA did. Both dBA and NdBA arrested cell proliferation at G0/G1, NdBA showing the greater effect. NdBA also induced a greater degree of cytotoxicity in A549 cells, but it had an insignificant cytotoxic effect in normal L6 cells. The results of flow cytometric, cytogenetial and histopathological studies in mice revealed that NdBA caused less nuclear condensation and DNA damage than dBA did. TEM images showed the presence of NdBA in brain samples of NdBA fed mice, indicating its ability to cross the BBB. Conclusion: Thus, compared to dBA, NdBA appears to have greater chemoprotective potential against lung cancer.

• Bulletin of the Korean Chemical Society
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• v.26 no.11
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• pp.1728-1734
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• 2005

The interactions of Cu(II)-meso-Tetrakis(n-N-methylpyridiniumyl)porphyrin (n = 2,3,4), respectively referred to as o-, m- and p-CuTMPyP, and DNA, poly$[d(A-T)_2]$ and poly$[d(G-C)_2]$ were investigated by circular and linear dichroism (CD and LD). In the o-CuTMPyP case, in which the rotation of the pyridinium ring is prevented, the shape of the CD spectrum when associated to DNA and poly$[d(A-T)_2]$ resembles and is characterized by a positive band at a low drug to DNA concentration ratio (R ratio) and is bisignate at a high R ratio. The former CD spectrum shape has been attributed to porphyrin that is bound monomerically outside of DNA while the latter can be attributed to those that are stacked. When o-CuTMPyP is bound to poly$[d(G-C)_2]$, the excitonic CD appeared at a relatively high R ratio. In contrast, a characteristic negative CD band in the Soret region was apparent for both m- and p-CuTMPyP when bound to DNA and poly$[d(G-C)_2]$ at the low R ratios, indicating that the porphyrin molecule intercalates. However, the DNA is bent near the intercalation site and the plane of the porphyrin molecule tilts relative to the DNA helix axis, as judged by the magnitude of the reduced LD. Various stacking patterns were identified by the shape of the CD spectrum for m- and p-CuTMPyP when bound to poly$[d(A-T)_2]$. Three species for the former complex and two for the latter complex were found which may reflect the extent of the stacking.

• Journal of Pharmaceutical Investigation
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• v.41 no.2
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• pp.95-102
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• 2011

An amphiphilic cationic branched methoxy poly (ethylene glycol)-branched polyethylenimine - poly(L-phenylalanine) (mPEG-bPEI-pPhe) block copolymer was successfully synthesized by ring-opening polymerization (ROP) of N-carboxyanhydride of L-phenylalanine (Phe-NCA) with mPEG-bPEI for the preparation of more stable polyelectrolyte complex (PEC) included a hydrophobic interaction. mPEG-bPEI was firstly prepared by the coupling of mPEG and bPEI using hexamethylene diisocyanate (HMDI). The structural properties of mPEG-bPEI-pPhe copolymers were confirmed by $^1H$ NMR. The copolymers exhibited a self-assemble behavior in water above critical aggregate concentration (CAC) in the range of 0.01-0.14 g/L. The CAC of copolymers obviously depended on the hydrophobic block content in the copolymers (the value decreased with the increase of the pPhe block content). The cationic copolymers have the ability to form multi-interaction complex (MIC) with bovine serum albumin (BSA) and plasmid DNA through multi-interaction (electrostatic and hydrophobic interaction). The physicochemical characterization of the complex was carried out by the measurement of zeta potential and particle size. Their zeta-potentials were positive (approximately +10 mV) and their sizes decreased with increasing pPhe contents in the copolymers (PPF/BSA wt% ratio = 2). The complex showed good stability at high ionic strength. Therefore, mPEG-bPEI-pPhe block copolymer was considered as a potential material to enhance the stability of complex including biotherapuetic drugs.

• Bulletin of the Korean Chemical Society
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• v.28 no.12
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• pp.2203-2208
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• 2007

Three possible binding modes of cationic meso-tetrakis(N-methylpyridinium-4-yl)porphyrin (TMPyP) to d[(GCATATATGC)2] duplex were investigated by the molecular dynamics (MD) simulation. Among the three binding modes namely, “along the groove”, “across the groove” and “face on the groove”, the “across the groove” model exhibited the largest negative binding free energy and the DNA backbone remained as the B form. In this model, the molecular plain of the TMPyP tilts 45o with respect to the DNA helix axis and is largely exposed to the solvent. TMPyP was stabilized mainly by the interaction between the positively charged neighboring pyridinium moieties of TMPyP and negatively charged phosphate groups of DNA. The result obtained in this work by MD and the report (Jin, B. et al., J. Am. Chem. Soc. 2005, 127, 2417.) that the spectral properties of poly[d(A-T)2] bound TMPyP in the presence and absence of the minor groove binding drug 4',6- diamidino-2-phenylindole are similar, we propose that TMPyP bind across the minor groove of the AT rich- DNA.

• Genomics & Informatics
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• v.11 no.4
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• pp.289-291
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• 2013

Human papillomavirus (HPV) infection is the leading cause of cancer mortality among women worldwide. The molecular understanding of HPV proteins has significant connotation for understanding their intrusion in the host and designing novel protein vaccines and anti-viral agents, etc. Genomic, proteomic, structural, and disease-related information on HPV is available on the web; yet, with trivial annotations and more so, it is not well customized for data analysis, host-pathogen interaction, strain-disease association, drug designing, and sequence analysis, etc. We attempted to design an online reserve with comprehensive information on HPV for the end users desiring the same. The Human Papillomavirus Proteome Database (hpvPDB) domiciles proteomic and genomic information on 150 HPV strains sequenced to date. Simultaneous easy expandability and retrieval of the strain-specific data, with a provision for sequence analysis and exploration potential of predicted structures, and easy access for curation and annotation through a range of search options at one platform are a few of its important features. Affluent information in this reserve could be of help for researchers involved in structural virology, cancer research, drug discovery, and vaccine design.

• Mass Spectrometry Letters
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• v.14 no.3
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• pp.116-119
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• 2023

Gynostemma pentaphyllum (Thunb.) Makino extract, a natural product with a history of traditional use, has gained attention for its potential health benefits. This study aimed to investigate its effects on key cytochrome P450 (CYP) enzymes using LC-MS/MS. Human liver microsomes and cDNA-expressed CYP2C8, CYP2C9, CYP2C19, and CYP3A4 supersomes were employed. Enzyme activity was assessed based on the formation of CYP-specific marker metabolites. The resulting data showed that the extract exhibited inhibitory effects on CYP2C8, CYP2C9, CYP2C19, and CYP3A4. Thus, G. pentaphyllum extract may influence the pharmacokinetics of drugs metabolized by CYP2C8, CYP2C9, CYP2C19, and CYP3A4. These findings emphasize the importance of considering potential herb-drug interactions when incorporating this extract into therapeutic regimens or dietary supplements.

• Genomics & Informatics
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• v.21 no.3
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• pp.42.1-42.23
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• 2023

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, one of the most deadly infections in humans. The emergence of multidrug-resistant and extensively drug-resistant Mtb strains presents a global challenge. Mtb has shown resistance to many frontline antibiotics, including rifampicin, kanamycin, isoniazid, and capreomycin. The only licensed vaccine, Bacille Calmette-Guerin, does not efficiently protect against adult pulmonary tuberculosis. Therefore, it is urgently necessary to develop new vaccines to prevent infections caused by these strains. We used a subtractive proteomics approach on 23 virulent Mtb strains and identified a conserved membrane protein (MmpL4, NP_214964.1) as both a potential drug target and vaccine candidate. MmpL4 is a non-homologous essential protein in the host and is involved in the pathogen-specific pathway. Furthermore, MmpL4 shows no homology with anti-targets and has limited homology to human gut microflora, potentially reducing the likelihood of adverse effects and cross-reactivity if therapeutics specific to this protein are developed. Subsequently, we constructed a highly soluble, safe, antigenic, and stable multi-subunit vaccine from the MmpL4 protein using immunoinformatics. Molecular dynamics simulations revealed the stability of the vaccine-bound Tolllike receptor-4 complex on a nanosecond scale, and immune simulations indicated strong primary and secondary immune responses in the host. Therefore, our study identifies a new target that could expedite the design of effective therapeutics, and the designed vaccine should be validated. Future directions include an extensive molecular interaction analysis, in silico cloning, wet-lab experiments, and evaluation and comparison of the designed candidate as both a DNA vaccine and protein vaccine.

• Genomics & Informatics
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• v.12 no.2
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• pp.64-70
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• 2014

Human papillomavirus (HPV) infection is the leading cause of cancer mortality among women worldwide. The life-threatening infection caused by HPV demands the need for designing anticancerous drugs. In the recent years, different compounds from natural origins, such as carrageenan, curcumin, epigallocatechin gallate, indole-3-carbinol, jaceosidin, and withaferin, have been used as a hopeful source of anticancer therapy. These compounds have been shown to suppress HPV infection by different researchers. In the present study, we explored these natural inhibitors against E6 oncoprotein of high-risk HPV-16, which is known to inactivate the p53 tumor suppressor protein. A robust homology model of HPV-16 E6 was built to anticipate the interaction mechanism of E6 oncoprotein with natural inhibitory molecules using a structure-based drug designing approach. Docking analysis showed the interaction of these natural compounds with the p53-binding site of E6 protein residues 113-122 (CQKPLCPEEK) and helped the restoration of p53 functioning. Docking analysis, besides helping in silico validation of natural compounds, also helps understand molecular mechanisms of protein-ligand interactions.

• Korean Chemical Engineering Research
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• v.44 no.1
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• pp.1-9
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• 2006

Biodevices composed of biomolecular layer by mimicking the natural functions of cells and the interaction mechanisms of the constituted biomolecules have been developed in various industrial fields such as medical diagnosis, drug screening, electronic device, bioprocess, and environmental pollution detection. To construct biodevices such as bioelectronic devices (biomolecular diode, bio-information storage device and bioelectroluminescence device), protein chip, DNA chip, and cell chip, biomolecules including DNA, protein, and cells have been used. Fusion technology consisting of immobilization technology of biomolecules, micro/nano-scale patterning, detection technology, and MEMs technology has been used to construct the biodevices. Recently, nanotechnology has been applied to construct nano-biodevices. In this paper, the current technology status of biodevice including its fabrication technology and applications is described and the future development direction is proposed.