• BMB Reports
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• v.49 no.4
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• pp.201-207
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• 2016

The CRISPR-Cas system has emerged as a fascinating and important genome editing tool. It is now widely used in biology, biotechnology, and biomedical research in both academic and industrial settings. To improve the specificity and efficiency of Cas nucleases and to extend the applications of these systems for other areas of research, an understanding of their precise working mechanisms is crucial. In this review, we summarize current studies on the molecular structures and dynamic functions of type I and type II Cas nucleases, with a focus on target DNA searching and cleavage processes as revealed by single-molecule observations.

• Nuclear Medicine and Molecular Imaging
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• v.42 no.3
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• pp.185-191
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• 2008

While indirect targeting strategies using reporter-genes are taking center stage in current molecular imaging research, another vital strategy has long involved direct imaging of specific receptors using radiolabeled ligands. Recently, there is renewal of immense interest in this area with particular attention to the epidermal growth factor receptor (EGFR), a transmembrane glycoprotein critically involved in the regulation of many cellular functions and malignancies. Recently, two novel classes of EGFR-targeting anticancer drugs have entered clinical trials with great expectations. These are monoclonal antibodies such as cetuximab that target the extracellular domain, and small molecule tyrosine kinase inhibitors such as gefitinib (lressa) and erlotinib (Tarceva) that target the catalytic domain of the receptor. However, early results have showed disappointing survival benefits, disclosing a major challenge for this therapeutic strategy; namely, the need to identify tumors that are most likely to respond to the agents. To address this important clinical issue, several noninvasive imaging techniques are under investigation including radiolabeled probes based on small molecule tyrosine kinase inhibitors, anti-EGFR antibodies, and EGF peptides. This review describes the current status, limitations, and future prospects in the development of radiotracer methods for EGFR imaging.

• The Korean Journal of Pesticide Science
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• v.9 no.3
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• pp.191-198
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• 2005

Hippuryl-L-histidyl-L-leucine (Hip-L-His-L-Leu, HHL) is the known substrate of ACE, which used often in inhibition kinetic study to design new inhibitor. Here we use HHL molecule as a template to predict pharmacophore which can interact with residues in active site of AnCE, new potential insecticide target protein. To explain physicochemical properties related to molecular geometry and conformational change in reaction field as well as electron density of atoms associated to pharmacophores, geometry optimization, NMR chemical shifts and natural population analysis were performed by ab initio and DFT method. Calculated NMR chemical shifts showed good agreement with the experimental ones and obtained electron densities were used for analyzing pharmacophores of corresponding atoms. Finally, we could extract aye pharmacophores related to hydrophobic aliphatic and aromatic site, hydrogen bonding donor and acceptor site and Zn binding site from the HHL molecule.

• Molecules and Cells
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• v.42 no.10
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• pp.729-738
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• 2019

Autophagy is an important process for protein recycling. Oligomerization of p62/SQSTM1 is an essential step in this process and is achieved in two steps. Phox and Bem1p (PB1) domains can oligomerize through both basic and acidic surfaces in each molecule. The ZZ-type zinc finger (ZZ) domain binds to target proteins and promotes higher-oligomerization of p62. This mechanism is an important step in routing target proteins to the autophagosome. Here, we determined the crystal structure of the PB1 homo-dimer and modeled the p62 PB1 oligomers. These oligomer models were represented by a cylindrical helix and were compared with the previously determined electron microscopic map of a PB1 oligomer. To accurately compare, we mathematically calculated the lead length and radius of the helical oligomers. Our PB1 oligomer model fits the electron microscopy map and is both bendable and stretchable as a flexible helical filament.

• Journal of Cancer Prevention
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• v.22 no.4
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• pp.203-210
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• 2017

After transcription, RNAs are always associated with RNA binding proteins (RBPs) to perform biological activities. RBPs can interact with target RNAs in sequence- and structure-dependent manner through their unique RNA binding domains. In development and progression of carcinogenesis, RBPs are aberrantly dysregulated in many human cancers with various mechanisms, such as genetic alteration, epigenetic change, noncoding RNA-mediated regulation, and post-translational modifications. Upon deregulation in cancers, RBPs influence every step in the development and progression of cancer, including sustained cell proliferation, evasion of apoptosis, avoiding immune surveillance, inducing angiogenesis, and activating metastasis. To develop therapeutic strategies targeting RBPs, RNA interference-based oligonucleotides or small molecule inhibitors have been screened based on reduced RBP-RNA interaction and changed level of target RNAs. Identification of binding RNAs with high-throughput techniques and integral analysis of multiple datasets will help us develop new therapeutic drugs or prognostic biomarkers for human cancers.

• Journal of the Korea Institute of Military Science and Technology
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• v.17 no.6
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• pp.828-835
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• 2014

GC-TSQ CI technique was applied for analysis of samples for the $32^{nd}$ OPCW proficiency test. Eight chemical weapon convention(CWC) related chemicals were identified by product ion mode analysis with GC-TSQ in the samples. Choice of specific precursor ion made it possible to supply selective total ion chromatograms(TICs) of target molecule. GC-TSQ CI anaylsis technique was useful method for chemical warfare agent verification because analysis selectivity was improved by choice of mother molecule as precursor ion and gave mass spectra.

• CELLMED
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• v.8 no.2
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• pp.8.1-8.5
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• 2018

Nitric oxide (NO) is a small diffusible molecule which plays an important role in various physiological activities. NO is a notable molecule, functioning as a cytotoxic agent and cellular messenger. There has been considerable interest in NO production by activated macrophages because this gaseous metabolite plays a fundamental role in the cytotoxic and cytostatic effects of macrophages towards invasive micro-organisms and tumour cells. No is a bioactive free radical that has been implicated in many physiological functions, plays a critical role during inflammation and therefore constitutes a potential target for developing therapeutics for inflammatory diseases. The use of medicinal plants by the population has been an important alternative the resource in the treatment of various diseases. Its growing acceptance in the medical community has been due to the fact that several plants with biological activities have been scientifically investigated and their efficacy and safety have been proven. In this review, discussed suppressive effects of No production by traditional medicines in RAW 264.7 and THP-1 macrophages.

• BMB Reports
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• v.32 no.2
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• pp.103-111
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• 1999

Hh proteins represent a new signaling paradigm in metazoan development. In species ranging from fruit flies to humans, Hh proteins mediate multiple processes vital to appropriate pattern formation in the developing embryo. Hh proteins undergo an autoprocessing event in which the full-length protein is cleaved into N-terminal and C-terminal domains (Hh-N and Hh-C, respectively), and a cholesterol moiety becomes covalently attached to Hh-N. All known signaling activities of Hh proteins are mediated by Hh-N while both the cleavage and cholesterol transfer reactions are mediated by Hh-C. The cholesterol attached to Hh-N is required to retrict the range of Hh signaling and may be involved in ensuring appropriate reception of the Hh signal in target tissues. Disruptions of Hh signaling pathways lead to severe developmental defects in newborns and cancers in adults. While studies of Hh proteins have yielded a wealth of new insight into the molecular mechanisms of metazoan development, many outstanding questions concerning Hh signaling mechanisms ensure that unraveling the secrets of this molecule will keep scientists well entertained for the foreseeable future.

• Journal of the Korean Magnetic Resonance Society
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• v.18 no.1
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• pp.10-14
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• 2014

Hsp90 is a good drug target molecule that is involved in regulating various signaling pathway in normal cell and the role of Hsp90 is highly emphasized especially in cancer cells. Thus, much efforts for discovery and development of Hsp90 inhibitor have been continued and a few Hsp90 inhibitors targeting the N-terminal ATP binding site are being tested in the clinical trials. There are no metabolic signature molecules that can be used to evaluate the effect of Hsp90 inhibition. We previously found a potential C-domain binder named PPC1 that is a synthetic small molecule. Here we report the metabolomics study to find signature metabolites upon treatment of PPC1 compound in lung cancer cell line, A549 and discuss the potentiality of metabolomic approach for evaluation of hit compounds.

• Toxicological Research
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• v.24 no.2
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• pp.93-100
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• 2008

Targeting protein kinases has been active area in drug discovery. The c-Jun N-terminal kinases(JNKs) have also been target for development of novel therapy in various diseases, since the roles of JNK signaling in pathological conditions were revealed in studies using jnk-deficient mice. Small molecule inhibitors and peptide inhibitors are identified for therapeutic intervention of JNK signaling pathway. SP-600125, an anthrapyrazole small molecule inhibitor for JNK with high potency and selectivity has been widely used for dissecting JNK signaling pathway. CC-401 is the first JNK inhibitor that went into clinical trial for inflammation and leukemia. Inhibitor for mixed lineage kinase (MLK), CEP-1347 also negatively regulates JNK signaling, and tried for potential use in Parkinson's disease. Cell-permeable peptide inhibitor D-JNKI-1 is being developed for the treatment of hearing loss. The current status of these JNK inhibitors and safety issue is discussed in the minireview.