• BMB Reports
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• v.43 no.11
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• pp.711-719
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• 2010

Kinomics is an emerging and promising approach for deciphering kinomes. Chemical kinomics is a discipline of chemical genomics that is also referred to as "chemogenomics", which is derived from chemistry and biology. Chemical kinomics has become a powerful approach to decipher complicated phosphorylation-based cellular signaling networks with the aid of small molecules that modulate kinase functions. Moreover, chemical kinomics has played a pivotal role in the field of kinase drug discovery as it enables identification of new molecular targets of small molecule kinase modulators and/or exploitation of novel functions of known kinases and has also provided novel chemical entities as hit/lead compounds. In this short review, contemporary chemical kinomics technologies such as activity-based protein profiling, T7 kinasetagged phages, kinobeads, three-hybrid systems, fluorescenttagged kinase binding assays, and chemical genomic profiling are discussed along with a novel allosteric Bcr-Abl kinase inhibitor (GNF-2/GNF-5) as a successful application of chemical kinomics approaches.

• Bulletin of the Korean Chemical Society
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• v.31 no.6
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• pp.1474-1478
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• 2010

An efficient method for labeling individual proteins in live cells is required for investigations into biological mechanisms and cellular processes. Here we describe the preparation of small quantum dots (QDs) that target membrane surface proteins bearing a hexahistidine-tag ($His_6$-tag) via specific binding to an nitrilotriacetic acid complex of nickel(II) ($NTA{\cdot}Ni^{2+}$) on the QD surfaces. We showed that the $NTA{\cdot}Ni^{2+}$-QDs bound to His-tag functionalized beads as a cellular mimic with high specificity and that QDs successfully targeted $His_6$-tagged vesicle-associated membrane proteins (VMAP) on cell surfaces. This strategy provides an efficient approach to monitoring synaptic protein dynamics in spatially restricted and confined biological environments.

• BMB Reports
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• v.51 no.12
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• pp.642-647
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• 2018

Ubiquitin-conjugating enzyme E2S (UBE2S), a family of E2 protein in the ubiquitination process, is involved in development of various cancers. However, its role in lung adenocarcinoma, has not been well elucidated. In this report, we attempted to investigate expression and function of UBE2S in lung adenocarcinoma. Up-regulation of UBE2S at mRNA, and protein level, was observed in human cancer tissues and lung adenocarcinoma cells. Higher UBE2S expression correlated with poorer prognosis of lung adenocarcinoma patients. UBE2S expression was efficiently suppressed by lentivirus-mediated shRNA strategy in A549 cells, and UBE2S silencing led to reduced cell proliferation, colony formation, and enhanced apoptosis. Inverse results were observed, in UBE2S over-expressed H1299 cells. Microarray analysis indicated that a large number of genes were regulated by UBE2S, and p53 signaling pathway may be critical, to the role of UBE2S in cancer development. Together, UBE2S could be a potential target for lung adenocarcinoma.

• Journal of Integrative Natural Science
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• v.15 no.4
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• pp.153-161
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• 2022

c-Jun N-terminal kinases (JNKs) are members of MAPK family. Many genes can relay signals that promote inflammation, cell proliferation, or cell death which causes several diseases have been associated to mutations in the JNK gene family. The JNK2 gene is significantly more important in cancer development than the JNK1 and JNK3 genes. There are several different ways in which JNK2 contributes to breast cancer, and one of these is through its role in cell migration. As a result, this study's primary objective was to employ computational strategies to identify promising leads that potentially target the JNK2 protein in a strategy to alleviate breast cancer. We have derived these anticancer compounds from marine brown seaweed called Turbinaria conoides. We have identified compounds Ethane, 1, 1-diethoxy- and Butane, 2-ethoxy as promising anti-cancer drugs by molecular docking, DFT, and ADME study.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.7 no.2
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• pp.153-159
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• 2021

This article provides an efficient ¹⁸F-labeling protocol based on a rapid condensation reaction between 2-cyanobenzothiazole (CBT) and N-terminal cysteine-containing biomolecules. The ¹⁸F-labeled CBT (¹⁸F-1) was prepared by radiofluorination of the tosylated precursor 4 with 18-crown-6/K+/[¹⁸F]F- complex. Using the purified ¹⁸F-1, ¹⁸F-labeled peptide (¹⁸F-7) and protein (¹⁸F-8) could be synthesized efficiently under mild conditions. This strategy would provide a convenient approach for rapid and site-specific ¹⁸F-labeling of various peptides and proteins for in vivo imaging and biomedical applications.

• Bulletin of the Korean Chemical Society
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• v.29 no.8
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• pp.1479-1484
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• 2008

Protein tyrosine phosphatase (PTP) 1B is the superfamily of PTPs and a negative regulator of multiple receptor tyrosine kinases (RTKs). Inhibition of protein tyrosine phosphatase 1B (PTP1B) has been proposed as a strategy for the treatment of type 2 diabetes and obesity. Recently, it has been reported that amentoflavone, a biflavonoid extracted from Selaginella tamariscina, inhibited PTP1B. In the present study, docking model between amentoflavone and PTP1B was determined using automated docking study. Based on this docking model and the interactions between the known inhibitors and PTP1B, we determined multiple pharmacophore maps which consisted of five features, two hydrogen bonding acceptors, two hydrogen bonding donors, and one lipophilic. Using receptor-oriented pharmacophore-based in silico screening, we searched the biflavonoid database including 40 naturally occurring biflavonoids. From these results, it can be proposed that two biflavonoids, sumaflavone and tetrahydroamentoflavone can be potent allosteric inhibitors, and the linkage at 5',8''-position of two flavones and a hydroxyl group at 4'-position are the critical factors for their allosteric inhibition. This study will be helpful to understand the mechanism of allosteric inhibition of PTP1B by biflavonoids and give insights to develop potent inhibitors of PTP1B.

• IMMUNE NETWORK
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• v.14 no.1
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• pp.7-13
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• 2014

Molecular mimicry is an attractive mechanism for triggering autoimmunity. In this review, we explore the potential role of evolutionary conserved bacterial proteins in the production of autoantibodies with focus on granulomatosis with polyangiitis (GPA) and rheumatoid arthritis (RA). Seven autoantigens characterized in GPA and RA were BLASTed against a bacterial protein database. Of the seven autoantigens, proteinase 3, type II collagen, binding immunoglobulin protein, glucose-6-phosphate isomerase, ${\alpha}$-enolase, and heterogeneous nuclear ribonuclear protein have well-conserved bacterial orthologs. Importantly, those bacterial orthologs are also found in human-associated bacteria. The wide distribution of the highly conserved stress proteins or enzymes among the members of the normal flora and common infectious microorganisms raises a new question on how cross-reactive autoantibodies are not produced during the immune response to these bacteria in most healthy people. Understanding the mechanisms that deselect auto-reactive B cell clones during the germinal center reaction to homologous foreign antigens may provide a novel strategy to treat autoimmune diseases.

• Journal of Periodontal and Implant Science
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• v.41 no.2
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• pp.54-59
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• 2011

Purpose: The aim of this study was to define the immunoreactive specificity of Porphyromonas gingivalis (P. gingivalis) heat shock protein (HSP) 60 in periodontitis and atherosclerosis. Methods: In an attempt to define the cross-reactive bacterial heat-shock protein with human self-antigen at molecular level, we have introduced a novel strategy for cloning hybridoma producing anti-P. gingivalis HSP 60 which is polyreactive to bacterial HSPs or to the human homolog. Results: Five cross-reactive clones were obtained which recognized the #19 peptide (TLVVNRLRGSLKICAVKAPG) among 37 synthetic peptides (20-mer, 5 amino acids overlapping) spanning the whole molecule of P. gingivalis HSP 60. We have also established three anti-P. gingivalis HSP 60 monoclonal antibodies demonstrating mono-specificity. These clones recognized the #29 peptide (TVPGGGTTYIRAIAALEGLK). Conclusions: Peptide #19 and #29 of P. gingivalis HSP 60 might be important immunoreactive epitopes in the immuno-pathogenic mechanism of bacterial antigen-triggered autoimmune diseases.

• BMB Reports
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• v.48 no.8
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• pp.445-453
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• 2015

Endoplasmic Reticulum (ER) is an organelle where most secretory and membrane proteins are synthesized, folded, and undergo further maturation. As numerous conditions can perturb such ER function, eukaryotic cells are equipped with responsive signaling pathways, widely referred to as the Unfolded Protein Response (UPR). Chronic conditions of ER stress that cannot be fully resolved by UPR, or conditions that impair UPR signaling itself, are associated with many metabolic and degenerative diseases. In recent years, Drosophila has been actively employed to study such connections between UPR and disease. Notably, the UPR pathways are largely conserved between Drosophila and humans, and the mediating genes are essential for development in both organisms, indicating their requirement to resolve inherent stress. By now, many Drosophila mutations are known to impose stress in the ER, and a number of these appear similar to those that underlie human diseases. In addition, studies have employed the strategy of overexpressing human mutations in Drosophila tissues to perform genetic modifier screens. The fact that the basic UPR pathways are conserved, together with the availability of many human disease models in this organism, makes Drosophila a powerful tool for studying human disease mechanisms. [BMB Reports 2015; 48(8): 445-453]

• Biomolecules & Therapeutics
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• v.26 no.3
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• pp.313-321
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• 2018

Anti-cancer drug resistance is a major problem in colorectal cancer (CRC) research. Although several studies have revealed the mechanism of cancer drug resistance, molecular targets for chemotherapeutic combinations remain elusive. To address this issue, we focused on the expression of cellular prion protein ($PrP^C$) in 5-FU-resistant CRC cells. In 5-FU-resistant CRC cells, $PrP^C$ expression is significantly increased, compared with that in normal CRC cells. In the presence of 5-FU, $PrP^C$ increased CRC cell survival and proliferation by maintaining the activation of the PI3K-Akt signaling pathway and the expression of cell cycle-associated proteins, including cyclin E, CDK2, cyclin D1, and CDK4. In addition, $PrP^C$ inhibited the activation of the stress-associated proteins p38, JNK, and p53. Moreover, after treatment of 5-FU-resistant CRC cells with 5-FU, silencing of $PrP^C$ triggered apoptosis via the activation of caspase-3. These results indicate that $PrP^C$ plays a key role in CRC drug resistance. The novel strategy of combining chemotherapy with $PrP^C$ targeting may yield efficacious treatments of colorectal cancer.