• Title/Summary/Keyword: Chemical genomics

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Whole Genome Analysis of the Red-Crowned Crane Provides Insight into Avian Longevity

  • Lee, HyeJin;Kim, Jungeun;Weber, Jessica A.;Chung, Oksung;Cho, Yun Sung;Jho, Sungwoong;Jun, JeHoon;Kim, Hak-Min;Lim, Jeongheui;Choi, Jae-Pil;Jeon, Sungwon;Blazyte, Asta;Edwards, Jeremy S.;Paek, Woon Kee;Bhak, Jong
    • Molecules and Cells
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    • v.43 no.1
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    • pp.86-95
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    • 2020
  • The red-crowned crane (Grus japonensis) is an endangered, large-bodied crane native to East Asia. It is a traditional symbol of longevity and its long lifespan has been confirmed both in captivity and in the wild. Lifespan in birds is known to be positively correlated with body size and negatively correlated with metabolic rate, though the genetic mechanisms for the red-crowned crane's long lifespan have not previously been investigated. Using whole genome sequencing and comparative evolutionary analyses against the grey-crowned crane and other avian genomes, including the long-lived common ostrich, we identified redcrowned crane candidate genes with known associations with longevity. Among these are positively selected genes in metabolism and immunity pathways (NDUFA5, NDUFA8, NUDT12, SOD3, CTH, RPA1, PHAX, HNMT, HS2ST1, PPCDC, PSTK CD8B, GP9, IL-9R, and PTPRC). Our analyses provide genetic evidence for low metabolic rate and longevity, accompanied by possible convergent adaptation signatures among distantly related large and long-lived birds. Finally, we identified low genetic diversity in the red-crowned crane, consistent with its listing as an endangered species, and this genome should provide a useful genetic resource for future conservation studies of this rare and iconic species.

Chemical kinomics: a powerful strategy for target deconvolution

  • Kim, Do-Hee;Sim, Tae-Bo
    • 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.

Discovery of Novel RNA Targets Using Chemical Genomics

  • Yu, Jae-Hoon
    • Proceedings of the PSK Conference
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    • 2003.10a
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    • pp.93-93
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    • 2003
  • RNA plays an important role in numerous biological processes but little is known about the interactions between small organic molecules and RNA. Our previous work has shown that the heterodimeric compound designed by conjugation with neomycin and loop-specific chemical bind to the stem-loop structured RNA motifs. In the present study, heterodimer was used, in a reverse way, as a probe to identify structured RNA motifs. (omitted)

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Molecular Modeling of Small Molecules as BVDV RNA-Dependent RNA Polymerase Allosteric Inhibitors

  • Chai, Han-Ha;Lim, Dajeong;Chai, Hee-Yeoul;Jung, Eunkyoung
    • Bulletin of the Korean Chemical Society
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    • v.34 no.3
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    • pp.837-850
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    • 2013
  • Bovine viral diarrhea virus (BVDV), a major pathogen of cattle, is a well-characterized pestivirus which has been used as a good model virus for HCV. The RNA-dependent RNA polymerase (RdRp) plays a key role in the RNA replication process, thus it has been targeted for antivirus drugs. We employed two-dimensional quantitative structure-activity relationship (2D-QSAR) and molecular field analysis (MFA) to identify the molecular substructure requirements, and the particular characteristics resulted in increased inhibitory activity for the known series of compounds to act as effective BVDV inhibitors. The 2D-QSAR study provided the rationale concept for changes in the structure to have more potent analogs focused on the class of arylazoenamines, benzimidazoles, and acridine derivatives with an optimal subset of descriptors, which have significantly contributed to overall anti-BVDV activity. MFA represented the molecular patterns responsible for the actions of antiviral compound at their receptors. We conclude that the polarity and the polarizability of a molecule play a main role in the inhibitory activity of BVDV inhibitors in the QSAR modeling.

β-Secretase (BACE1) Purification by Refolding Method and Complex with Hispidin

  • Lim, Ji-Hong;Lee, Bo Ram;Park, Hee Won;Hong, Bum Soo;Lim, Beong Ou;Kim, Young Jun
    • Journal of the Korean Chemical Society
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    • v.58 no.6
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    • pp.553-559
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    • 2014
  • Alzheimer's disease (AD) is a devastating neurodegenerative disease that represents the most common form of dementia among the elderly population. The deposition of aggregated ${\beta}$-amyloid ($A{\beta}$) senile plaques in the human brain is a classic observation in the neuropathology of AD, yet an understanding of the mechanism of their formation remains elusive. $A{\beta}$ is formed through endoproteolysis of the amyloid precursor protein (APP) by ${\beta}$-secretase (BACE1, ${\beta}$-site APP-cleaving enzyme) and ${\gamma}$-secretase. In this study, BACE1 protein was successfully over-expressed, purified, and refolded and utilized in a binding study with hispidin. We developed a simpler refolding method using a urea gradient and size-exclusion gel filtration to purify an active BACE1 protein variant, in larger quantities than that reported previously, and measured the binding affinity of hispidin to the BACE1 protein variant through isothermal titration calorimetry.

First detection of a G1-like H9N2 virus in Russia, 2018

  • Sharshov, Kirill;Kurskaya, Olga;Sobolev, Ivan;Leonov, Sergey;Kabilov, Marsel;Tatyana, Alikina;Alekseev, Alexander;Derko, Anastasiya;Yushkov, Yuriy;Saito, Takehiko;Uchida, Yuko;Mine, Junki;Irza, Victor;Shestopalov, Alexander
    • Korean Journal of Veterinary Research
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    • v.59 no.1
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    • pp.37-42
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    • 2019
  • Worldwide, avian influenza H9N2 viruses of different lineages are the most widespread viruses in poultry. However, to date, cases in Russia have not been documented. In this study, we report the first detection of a G1-like H9N2 virus from poultry sampled at live-bird markets in Russia (Far East region) during the winter of 2018 (isolate A/chicken/Amur_Russia/17/2018). We assume there has been further circulation of the A/chicken/Amur_Russia/17/2018 H9N2 virus in the Russian Far East with possible distribution to other regions or countries in 2018-2019.

Extract of high hydrostatic pressure-treated danshen (Salvia miltiorrhiza) ameliorates atherosclerosis via autophagy induction

  • Ko, Minjeong;Oh, Goo Taeg;Park, Jiyong;Kwon, Ho Jeong
    • BMB Reports
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    • v.53 no.12
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    • pp.652-657
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    • 2020
  • Danshen (Salvia miltiorrhiza) is a traditional medicinal plant widely used in Asian countries for its pharmacological activities (e.g., amelioration of cardiovascular diseases). In this study, we investigated the anti-atherosclerotic activity of raw danshen root extract prepared using high hydrostatic pressure (HHP) at 550 MPa for 5 min and hot water extraction. This method was useful for elimination of bacteria from cultured danshen plants and for better extraction yield of active principles. The HHP-treated danshen extract (HDE) inhibited proliferation of human umbilical vein endothelial cells (HUVECs) and induced autophagy that was assessed by LC3 conversion and p62 degradation. HDE suppressed foam cell formation in oxLDL-induced RAW264.7 macrophages; lysosomal activity simultaneously increased, measured by acridine orange staining. HDE also reduced atherosclerotic plaque development in vivo in apolipoprotein E knock-out (ApoE-/-) mice fed a high cholesterol diet. Taken together, these results indicated that HDE exhibited anti-atherosclerotic activity via autophagy induction.