• Macromolecular Research
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• v.15 no.5
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• pp.437-442
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• 2007

Poly(ethylene glycol) methyl ether (PEG)-poly(${\beta}$-amino ester) (PAE) block copolymers were synthesized using a Michael-type step polymerization, and the construction of pH-sensitive polymeric micelles (PM) investigated. The ${\beta}$-amino ester block of the block copolymers functioned as a pH-sensitive moiety as well as a hydrophobic block in relation to the ionization of PAE, while PEG acted as a hydrophilic block, regardless of ionization. The synthesized polymers were characterized using $^1H-NMR$, with their molecular weights measured using gel permeation chromatography. The $pK_b$ values of the pH-sensitive polymers were measured using a titration method. The pH-sensitivity and critical micelle concentration (CMC) of the block copolymers in PBS solution were estimated using fluorescence spectroscopy. The pH dependent micellization behaviors with various bisacrylate esters varied within a narrow pH range. The critical micelle concentration at pH 7.4 decreased from 0.032 to 0.004 mg/mL on increasing the number of methyl group in the bisacrylate from 4 to 10. Also, the particle size of the block copolymer micelles was determined using dynamic light scattering (DLS). The DLS results revealed the micelles had an average size below 100 nm. These pH-sensitive polymeric micelles may be good carriers for the delivery of an anticancer drug.

• BMB Reports
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• v.36 no.3
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• pp.299-304
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• 2003

For deciphering the cyclic guanosine monophosphate (cGMP) signaling pathway, we employed chemical proteomics to identify the novel target molecules of cGMP. We used cGMP that was immobilized onto agarose beads with linkers directed at three different positions of cGMP. We performed a pull-down assay using the beads as baits on tissue lysates and identified 9 proteins by MALDI-TOF (Matrix-Assisted Laser Desorption/Ionization Time-of-Flight) mass spectrometry. Some of the identified proteins were previously known cGMP targets, including cGMP-dependent protein kinase and cGMP-stimulated phosphodiesterase. Surprisingly, some of the co-precipitated proteins were never formerly reported to associate with the cGMP signaling pathway. The competition binding assays showed that the interactions are not by nonspecific binding to either the linker or bead itself, but by specific binding to cGMP. Furthermore, we observed that the interactions are highly specific to cGMP against other nucleotides, such as cyclic adenosine monophosphate (cAMP) and 5'-GMP, which are structurally similar to cGMP. As one of the identified targets, MAPK1 was confirmed by immunoblotting with an anti-MAPK1 antibody. For further proof, we observed that the membrane-permeable cGMP (8-bromo cyclic GMP) stimulated mitogen-activated protein kinase 1 signaling in the treated cells. Our present study suggests that chemical proteomics can be a very useful and powerful technique for identifying the target proteins of small bioactive molecules.

• Journal of Biomedical and Translational Research
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• v.19 no.4
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• pp.130-139
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• 2018

This study aimed to analyze a high-performance liquid chromatography (HPLC) separation using a pentafluorophenyl column of parent drug hydroxychloroquine (HCQ) and its active metabolite, desethylhydroxchloroquine (DHCQ) applying to determine bioequivalence of two different formulations administered to patients. A rapid, simple, sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for bioanalysis of HCQ and its metabolite DHCQ in human whole blood using deuterium derivative $hydroxychloroquine-D_4$ as an internal standard (IS). A triple-quadrupole mass spectrometer was operated using electrospray ionization in multiple reaction monitoring (MRM) mode. Sample preparation involves a two-step precipitation of protein techniques. The removed protein blood samples were chromatographed on a pentafluorophenyl (PFP) column ($50mm{\times}4.6mm$, $2.6{\mu}m$) with a mobile phase (ammonium formate solution containing dilute formic acid) in an isocratic mode at a flow rate of 0.45 mL/min. The standard curves were found to be linear in the range of 2 - 500 ng/mL for HCQ; 2 - 2,000 ng/mL for DHCQ in spite of lacking a highly sensitive MS spectrometry system. Results of intra- and inter-day precision and accuracy were within acceptable limits. A run time of 2.2 min for HCQ and 2.03 min for DHCQ in blood sample facilitated the analysis of more than 300 human whole blood samples per day. Taken together, we concluded that the assay developed herein represents a highly qualified technology for the quantification of HCQ in human whole blood for a parallel design bioequivalence study in a healthy male.

• Journal of Marine Bioscience and Biotechnology
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• v.14 no.1
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• pp.9-24
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• 2022

Low-molecular weight peptides derived from fish collagen exhibit several bioactivities, including antioxidant, antiwrinkle, antimicrobial, antidiabetic, and antihypertension effects. These peptides are also involved in triglyceride suppression and memory improvement. This study aimed to investigate the optimal processing condition for preparing low-molecular weight peptides from flounder skin, and the properties of the hydrolysate. The optimal processing conditions for peptic hydrolysis were as follows: a ratio of pepsin to dried skin powder of 2% (w/w), pH of 2.0, and a temperature of 50℃. Peptic hydrolysate contains several low-molecular weight peptides below 300 Da. Gly-Pro-Hyp(GPHyp) peptide, a process control index, was detected only in peptic hydrolysate on matrix-assisted laser desorption/ionization-time-of-flight(MALDI-TOF) spectrum. 2,2'-azinobis-(3-3-ethylbenzothiazolline-6- sulfonic acid(ABTS) radical scavenging activity of the peptic hydrolysate was comparable to that of 1 mM ascorbic acid, which was used as a positive control at pH 5.5, whereas collagenase inhibition was five times higher with the peptic hydrolysate than with 1 mM ascorbic acid at pH 7.5. However, the tyrosinase inhibition ability of the peptic hydrolysate was lower than that of arbutin, which was used as a positive control. The antibacterial effect of the peptic hydrolysate against Propionibacterium acne was not observed. These results suggest that the peptic hydrolysate derived from a flounder skin is a promising antiwrinkle agent that can be used in various food and cosmetic products to prevent wrinkles caused by ultraviolet radiations.

• Bulletin of the Korean Chemical Society
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• v.30 no.5
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• pp.1152-1156
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• 2009

Silent information regulator 2 (Sir2) or sirtuins are NAD(+)-dependent deacetylases, which hydrolyze the acetyllysine residues. In mammals, sirtuins are classified into seven different classes (SIRT1-7). SIRT1 was reported to be involved in age related disorders like obesity, metabolic syndrome, type II diabetes mellitus and Parkinson’s disease. Activation of SIRT1 is one of the promising approaches to treat these age related diseases. In this study, we have used HipHop module of CATALYST to identify a series of pharmacophore models to screen SIRT1 enhancing molecules. Three molecules from Sirtris Pharmaceuticals were selected as training set and 607 sirtuin activator molecules were used as test set. Five different hypotheses were developed and then validated using the training set and the test set. The results showed that the best pharmacophore model has four features, ring aromatic, positive ionization and two hydrogen-bond acceptors. The best hypothesis from our study, Hypo2, screened high number of active molecules from the test set. Thus, we suggest that this four feature pharmacophore model could be helpful to screen novel SIRT1 activator molecules. Hypo2-virtual screening against Maybridge database reveals seven molecules, which contains all the critical features. Moreover, two new scaffolds were identified from this study. These scaffolds may be a potent lead for the SIRT1 activation.

• Journal of Life Science
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• v.27 no.6
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• pp.708-725
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• 2017

Ionizing radiation is enough energy to interact with matter to remove orbital electrons, neutrons, and protons in the atom. Ionizing radiation like this leads to oxidizing metabolism that alter molecular structure through direct and indirect interactions of radiation with the deoxyribonucleic acid in the nucleus and cytoplasmic organelles or via products of cytoplasm radiolysis. These ionization can result in tissue damage and disruption of cellular function at the molecular level. Consequently, ionizing radiation-induced modifications of ion channels and transporters have been reported. When the harmful effects exceed those of homeostatic biochemical processes, induced biological changes persist and may be propagated to progeny cells. Also, Reactive oxygen species formed on the effect of ionizing radiation can get across into neighboring cells through the cell junctions that are responsible for intercellular chemical communication, and may there bring about changes characteristic to radiation damage. Depending on radiation dose, dose-rate and quality, these protective mechanisms may or may not be sufficient to cope with the stress. This paper briefly reviewed reports on ionization radiation effects on cellular level that support the concept of radiation biology. A better understanding of the biological effects of ionizing radiation will lead to better use of and better protection from radiation.

• Tuberculosis and Respiratory Diseases
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• v.61 no.1
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• pp.41-45
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• 2006

Background; Several clinical scoring systems are currently being used to predict the outcome of sepsis, but they all have certain limitations. Therefore, we sought to identify the proteomic biomarkers, with wsing proteomic tools, that differed according to the outcome of sepsis patients. Methods; Upon admission to the ICU, blood samples were obtained from the 16 patients with sepsis who were enrolled in this study. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI -TOF MS) was used to identify the markers that could predict the outcome of sepsis. Results; We found six peaks, by using cation and anion chips, that statistically differed between those patients who died and those who survived. Conclusion; The biomarkers we found by using proteomic tools may help predict the prognosis and also plan the treatment of sepsis.

• Applied Chemistry for Engineering
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• v.28 no.3
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• pp.263-271
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• 2017

The application of mass spectrometry to polymer science has rapidly increased since the development of MALDI-TOF MS. This review summarizes current polymer analysis methods using MALDI-TOF MS, which has been extensively applied to analyze the average molecular weight of biopolymers and synthetic polymers. Polymer sequences have also been analyzed to reveal the structures and composition of monomers. In addition, the analysis of unknown end-groups and the determination of polymer concentrations are very important applications. Hyphenated techniques using MALDI-tandem MS have been used for the analysis of fragmentation patterns and end-groups, and also the combination of SEC and MALDI-TOF MS techniques is recommended for the analysis of complex polymers. Moreover, MALDI-TOF MS has been utilized for the observation of polymer degradation. Ion mobility MS, TOF-SIMS, and MALDI-TOF-imaging are also emerging technologies for polymer characterization because of their ability to automatically fractionate and localize polymer samples. The determination of polymer characteristics and their relation to the material properties is one of the most important demands for polymer scientists; the development of software and instrument for higher molecular mass range (> 100 kD) will increase the applications of MALDI-TOF MS for polymer scientists.

• Korean Journal of Food Science and Technology
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• v.21 no.3
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• pp.391-398
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• 1989

Triglyceride molecular species In some vegetable oils were analyzed by capillary column gas chromatography and electron impact ionization mass spectrometry utilizing selected ion monitoring. Triglycerides were separated according to their molecular weights and their degrees of unsaturation on $25m{\times}0.25mm$ fused silica open tubular capillary column coated with a phenylmethylsilicone gum stationary phase and in an analysis time less than 13 min. Triglyceride molecular species were identified by analyzing the fragment ions having the same time on the selected ion monitoring profile . The major triglyceride molecular species in each oils were $C_{18:1}.\;C_{18:2}.\;C_{18:2}(OLL:18.3%),\;C_{18:2}.\;C_{18:2}.\;C_{18:2}(LLL;\;14.3%),\;C_{18:0}.\;C_{18:2}.\;C_{18:2}(SLL;\;14.1%),\;C_{16:0}.\;C_{18:2}.\;C_{18:2}(PLL;\;13.2%),\;C_{16:0}.\;C_{18:2}.\;C_{18:1}(PLO;\;11.6%)$ in corn oil, $C_{18:2}.\;C_{18:2}.\;C_{18:2}(LLL;\;18.0%),\;C_{18:1}.\;C_{18:2}.\;C_{18:2}(OLL;\;18.0%),\;C_{16:0}.\;C_{18:2}.\;C_{18:2}(PLL;\;17.1%)$ in safflower oil, $C_{16:0}.\;C_{18:2}.\;C_{18:2}(PLL;\;23.5%),\;C_{16:0}.\;C_{18:2}.\;C_{18:1}(PLO;\;13.8%),\;C_{18:0}.\;C_{18:1}.\;C_{18:1}(SOO;\;13.5%),\;C_{18:1}.\;C_{18:2}.\;C_{18:2}(OLL;\;10.6%)$ in cottonseed oil.

• Bulletin of the Korean Chemical Society
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• v.33 no.10
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• pp.3285-3292
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• 2012

The interaction of thiazole drug with (6,0) zigzag single-walled boron nitride nanotube of finite length in gas and solvent phases was studied by means of density functional theory (DFT) calculations. In both phases, the binding energy is negative and presenting characterizes an exothermic process. Also, the binding energy in solvent phase is more than that the gas phase. Binding energy corresponding to adsorption of thiazole on the BNNT model in the gas and solvent phases was calculated to be -0.34 and -0.56 eV, and about 0.04 and 0.06 electrons is transferred from the thiazole to the nanotube in the phases. The significantly changes in binding energies and energy gap values by the thiazole adsorption, shows the high sensitivity of the electronic properties of BNNT towards the adsorption of the thiazole molecule. Frontier molecular orbital theory (FMO) and structural analyses show that the low energy level of LUMO, electron density, and length of the surrounding bonds of adsorbing atoms help to the thiazole adsorption on the nanotube. Decrease in global hardness, energy gap and ionization potential is due to the adsorption of the thiazole, and consequently, in the both phases, stability of the thiazole-attached (6,0) BNNT model is decreased and its reactivity increased. Presence of polar solvent increases the electron donor of the thiazole and the electrophilicity of the complex. This study may provide new insight to the development of functionalized boron nitride nanotubes as drug delivery systems for virtual applications.