• Title/Summary/Keyword: Molecular Recognition

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Innate immune recognition of respiratory syncytial virus infection

  • Kim, Tae Hoon;Lee, Heung Kyu
    • BMB Reports
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    • v.47 no.4
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    • pp.184-191
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    • 2014
  • Respiratory syncytial virus (RSV) is the leading cause of respiratory infection in infants and young children. Severe clinical manifestation of RSV infection is a bronchiolitis, which is common in infants under six months of age. Recently, RSV has been recognized as an important cause of respiratory infection in older populations with cardiovascular morbidity or immunocompromised patients. However, neither a vaccine nor an effective antiviral therapy is currently available. Moreover, the interaction between the host immune system and the RSV pathogen during an infection is not well understood. The innate immune system recognizes RSV through multiple mechanisms. The first innate immune RSV detectors are the pattern recognition receptors (PRRs), including toll-like receptors (TLRs), retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), and nucleotide-biding oligomerization domain (NOD)-like receptors (NLRs). The following is a review of studies associated with various PRRs that are responsible for RSV virion recognition and subsequent induction of the antiviral immune response during RSV infection.

Liquid Chromatographic Reaolution of N-Protected α -Amino Acids as Their Anilide and 3,5-Dimethylanilide Derivatives on Chiral Syationary Phases Derived fron (S)-Leucine

  • Hyun, Myung-Ho;Cho, Yoon-Jae;Baik, In-Kyu
    • Bulletin of the Korean Chemical Society
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    • v.23 no.9
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    • pp.1291-1294
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    • 2002
  • Various racemic N-protected ${\alpha}-amino$ acids such as N-t-BOC-(tert-butoxycarbonyl), N-CBZ-(benzyloxycarbonyl) and N-FMOC-(9-fluorenylmethyloxycarbonyl) ${\alpha}-amino$ acids were resolved as their anilide and 3,5-dimethylanilde derivatives on an HPLC chira l stationary phase (CSP) developed by modifying a commercial (S)-leucine CSP. The chromatographic resolution results were compared to those on the commercial (S)-leucine CSP. The resolutions were greater on the modified CSP than those on the commercial CSP with only one exception, the resolution of N-t-BOC-phenylglycine anilide. In addition, the chromatographic resolution behaviors were quite consistent except for the resolution of N-protected phenylglycine derivatives, the (S)-enantiomers being retained longer. Based on the chromatographic resolution behaviors and with the aid of CPK molecular model studies, we proposed a chiral recognition mechanism for the resolution of N-protected ${\alpha}-amino$ acid derivatives. However, for the resolution of N-protected phenylglycine derivatives, a second chiral recognition mechanism, which competes in the opposite sense with the first chiral recognition mechanism, was proposed. The two competing chiral recognition mechanisms were successfully used in the rationalization of the chromatographic behaviors for the resolution of N-protected phenylglycine derivatives.

Discovery of 14-3-3 zeta as a potential biomarker for cardiac hypertrophy

  • Joyeta Mahmud;Hien Thi My Ong;Eda Ates;Hong Seog Seo;Min-Jung Kang
    • BMB Reports
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    • v.56 no.6
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    • pp.341-346
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    • 2023
  • Acute myocardial infarction (AMI) is a multifaceted syndrome influenced by the functions of various extrinsic and intrinsic pathways and pathological processes, which can be detected in circulation using biomarkers. In this study, we investigated the secretome protein profile of induced-hypertrophy cardiomyocytes to identify next-generation biomarkers for AMI diagnosis and management. Hypertrophy was successfully induced in immortalized human cardiomyocytes (T0445) by 200 nM ET-1 and 1 μM Ang II. The protein profiles of hypertrophied cardiomyocyte secretomes were analyzed by nano-liquid chromatography with tandem mass spectrometry and differentially expressed proteins that have been identified by Ingenuity Pathway Analysis. The levels of 32 proteins increased significantly (>1.4 fold), whereas 17 proteins (<0.5 fold) showed a rapid decrease in expression. Proteomic analysis showed significant upregulation of six 14-3-3 protein isoforms in hypertrophied cardiomyocytes compared to those in control cells. Multi-reaction monitoring results of human plasma samples showed that 14-3-3 protein-zeta levels were significantly elevated in patients with AMI compared to those of healthy controls. These findings elucidated the role of 14-3-3 protein-zeta in cardiac hypertrophy and cardiovascular disorders and demonstrated its potential as a novel biomarker and therapeutic strategy.

Design of a RANK-Mimetic Peptide Inhibitor of Osteoclastogenesis with Enhanced RANKL-Binding Affinity

  • Hur, Jeonghwan;Ghosh, Ambarnil;Kim, Kabsun;Ta, Hai Minh;Kim, Hyunju;Kim, Nacksung;Hwang, Hye-Yeon;Kim, Kyeong Kyu
    • Molecules and Cells
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    • v.39 no.4
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    • pp.316-321
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    • 2016
  • The receptor activator of nuclear factor ${\kappa}B$ (RANK) and its ligand RANKL are key regulators of osteoclastogenesis and well-recognized targets in developing treatments for bone disorders associated with excessive bone resorption, such as osteoporosis. Our previous work on the structure of the RANK-RANKL complex revealed that Loop3 of RANK, specifically the non-canonical disulfide bond at the tip, performs a crucial role in specific recognition of RANKL. It also demonstrated that peptide mimics of Loop3 were capable of interfering with the function of RANKL in osteoclastogenesis. Here, we reported the structure-based design of a smaller peptide with enhanced inhibitory efficiency. The kinetic analysis and osteoclast differentiation assay showed that in addition to the sharp turn induced by the disulfide bond, two consecutive arginine residues were also important for binding to RANKL and inhibiting osteoclastogenesis. Docking and molecular dynamics simulations proposed the binding mode of the peptide to the RANKL trimer, showing that the arginine residues provide electrostatic interactions with RANKL and contribute to stabilizing the complex. These findings provided useful information for the rational design of therapeutics for bone diseases associated with RANK/RANKL function.

High Efficiency Binding Aptamers for a Wide Range of Bacterial Sepsis Agents

  • Graziani, Ana Claudia;Stets, Maria Isabel;Lopes, Ana Luisa Kalb;Schluga, Pedro Henrique Caires;Marton, Soledad;Ferreira, Ieda Mendes;de Andrade, Antero Silva Ribeiro;Krieger, Marco Aurelio;Cardoso, Josiane
    • Journal of Microbiology and Biotechnology
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    • v.27 no.4
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    • pp.838-843
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    • 2017
  • Sepsis is a major health problem worldwide, with an extremely high rate of morbidity and mortality, partly due to delayed diagnosis during early disease. Currently, sepsis diagnosis requires bacterial culturing of blood samples over several days, whereas PCR-based molecular diagnosis methods are faster but lack sensitivity. The use of biosensors containing nucleic acid aptamers that bind targets with high affinity and specificity could accelerate sepsis diagnosis. Previously, we used the systematic evolution of ligands by exponential enrichment technique to develop the aptamers Antibac1 and Antibac2, targeting the ubiquitous bacterial peptidoglycan. Here, we show that these aptamers bind to four gram-positive and seven gram-negative bacterial sepsis agents with high binding efficiency. Thus, these aptamers could be used in combination as biological recognition elements in the development of biosensors that are an alternative to rapid bacteria detection, since they could provide culture and amplification-free tests for rapid clinical sepsis diagnosis.

Quartz Crystal Microbalance Modified by a Novel Vapor Diffused Molecular Assembly Technique and Measurement of Chiral Mandelic Acid (기상확산 자기조립화법에 QCM수식과 Madelic Acid 키랄물질 측정)

  • Kim, JongMin;Kim, SeungJin;Woo, SunYoung;Jang, SukHee;Kim, Woo-Sik;Chang, SangMok
    • Korean Chemical Engineering Research
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    • v.48 no.5
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    • pp.574-582
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    • 2010
  • In this study, the possibility of a quartz crystal micro-balance(QCM) modification of crystallization of L-Penicillamine and D-Penicillamine with a Vapor Diffused Molecular Assembly Technique and its application to the R-(-)-Mandelic acid and S-(+)- Mandelic acid measurement was investigated. The 3-dimensional structures of L-Penicillamine and D-Penicillamine on the surface of QCM were verified to be different from each other through QCM and AFM analyses. The D-Penicillamine modified QCM had specific recognition to the R-(-)-Mandelic acid, but L-Penicillamine modified QCM had no specificity to the R-(-)-Mandelic acid and S-(+)- Mandelic acid. From these results, it was known that the QCM could be modified with various selective meterials via VDMA, and the chiral isomer such as a Mandelic acid isomer could be detected by using a modified QCM.

Synthesis and Anion Binding Affinities of Novel Molecular Tweezers Based on Chenodeoxycholic Acid Bearing Different Lengths of Arm

  • Kim, Ki-Soo;Jang, Hyun-Seok;Kim, Hong-Seok
    • Bulletin of the Korean Chemical Society
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    • v.27 no.9
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    • pp.1445-1449
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    • 2006
  • Molecular tweezers based on chenodeoxycholic acid bearing different lengths of arm were synthesized andtheir anion binding affinities were evaluated by $^1H$ NMR, isothermal calorimetric titration, and ESI mass spectrometry. Molecular tweezer 6 showed a high selectivity toward $H_2PO_4\;^-$ over $Cl^-,\;Br^-,\;I^-, $ and $CH_3CO_2\;^-$ by $^1H$ NMR titration, whereas the association constant for $F^-$ revealed the largest value as determined by ITC. The selectivity of 6 towards $F^-$ was about 103 times higher than that of $Cl^-,\;H_2PO_4\;^- $, and $CH_3CO_2\;^-$. ITCexperiment of 6 with $F^-$ in a DMSO showed two binding modes; two sequential association constants $K_1\;=\;2.77\;{\times}\;10^5\;M^{-1}$ and $K_2\;=\;8.68\;{\times}\;10^6\;M^{-1}$ were found. These sequential bindings were confirmed by ESI massspectrometry. 1 : 1 and 1 : 2 complexes of 6 and $F^-$ were found at m/z 868.08 and 884.04.

Viral Inhibition of PRR-Mediated Innate Immune Response: Learning from KSHV Evasion Strategies

  • Lee, Hye-Ra;Choi, Un Yung;Hwang, Sung-Woo;Kim, Stephanie;Jung, Jae U.
    • Molecules and Cells
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    • v.39 no.11
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    • pp.777-782
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    • 2016
  • The innate immune system has evolved to detect and destroy invading pathogens before they can establish systemic infection. To successfully eradicate pathogens, including viruses, host innate immunity is activated through diverse pattern recognition receptors (PRRs) which detect conserved viral signatures and trigger the production of type I interferon (IFN) and pro-inflammatory cytokines to mediate viral clearance. Viral persistence requires that viruses co-opt cellular pathways and activities for their benefit. In particular, due to the potent antiviral activities of IFN and cytokines, viruses have developed various strategies to meticulously modulate intracellular innate immune sensing mechanisms to facilitate efficient viral replication and persistence. In this review, we highlight recent advances in the study of viral immune evasion strategies with a specific focus on how Kaposi's sarcoma-associated herpesvirus (KSHV) effectively targets host PRR signaling pathways.

Morphological and molecular evidence for the recognition of Hypoglossum sabahense sp. nov. (Delesseriaceae, Rhodophyta) from Sabah, Malaysia

  • Wynne, Michael J.;Kamiya, Mitsunobu;West, John A.;Goer, Susan Loiseaux-de;Lim, Phaik-Eem;Sade, Ahemad;Russell, Hannah;Kupper, Frithjof C.
    • ALGAE
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    • v.35 no.2
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    • pp.157-165
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    • 2020
  • Culture isolates of the genus Hypoglossum (Delesseriaceae, Rhodophyta) were obtained and their development and morphological structure over many years were followed in the laboratory. Molecular data (rbcL, large subunit ribosomal DNA, and cytochrome c oxidase subunit I) were obtained from these strains and evidence presented to recognize the new species: Hypoglossum sabahense from Sabah, Malaysia. Because various aspects of morphology in culture specimens differ significantly from types based on field specimens we have to rely mainly on the molecular criteria in ascribing a new taxonomic name here. This also is complicated by the major lack of molecular phylogenetic evidence for Hypoglossum and other Delesseriaceae. The 'Germling Emergence Method' and 'serendipity' are proving valuable in discovering significant new taxa from laboratory cultures which otherwise might never be known.

Structural Control and Two-Dimensional Order of Organic Thiol Self-Assembled Monolayers on Au(111)

  • No, Jae-Geun
    • Proceedings of the Korean Vacuum Society Conference
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    • 2011.02a
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    • pp.26-26
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    • 2011
  • Self-assembled monolayers (SAMs) prepared by sulfur-containing organic molecules on metal surfaces have drawn much attention for more than two decades because of their technological applications in wetting, chemical and biosensors, molecular recognition, nanolithography, and molecular electronics. In this talk, we will present self-assembly mechanism and two-dimensional (2D) structures of various organic thiol SAMs on Au(111), which are mainly demonstrated by molecular-scale scanning tunneling microscopy (STM) observation. In addition, we will provide some idea how to control 2D molecular arrangements of organic SAMs. For instance, the formation and surface structure of pentafluorobenzenethiols (PFBT) self-assembled monolayers (SAMs) on Au(111) formed from various experimental conditions were examined by means of STM. Although it is well known that PFBT molecules on metal surfaces do not form ordered SAMs, we clearly revealed for the first time that adsorption of PFBT on Au(111) at $75^{\circ}C$ for 2 h yields long-range, well-ordered self-assembled monolayers having a $(2{\times}5\sqrt{13})R30^{\circ}$ superlattice. Benzenethiols (BT) SAMs on gold usually have disordered phases, however, we have clearly demonstrated that the displacement of preadsorbed cyclohexanethiol self-assembled monolayers (SAMs) on Au(111) by BT molecules can be a successful approach to obtain BT SAMs with long-range ordered domains. Our results will provide new insight into controlling the structural order of BT or PFBT SAMs, which will be very useful in precisely tailoring the interface properties of metal surfaces in electronic devices.

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