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Wyszukujesz frazę "small-molecule inhibitor" wg kryterium: Temat


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Tytuł:
Exploring Baltic Sea cyanobacteria for small-molecule inhibitors of microRNA function: a project description
Autorzy:
Brzuzan, P.
Mazur-Marzec, H.
Stefaniak, F.
Woźny, M.
Florczyk, M.
Powiązania:
https://bibliotekanauki.pl/articles/363294.pdf
Data publikacji:
2018
Wydawca:
Uniwersytet Warmińsko-Mazurski w Olsztynie
Tematy:
cyanobacteria
luciferase reporter cell line
microRNA
small-molecule inhibitor
cyjanobakteria
inhibitor
Morze Bałtyckie
Opis:
Cyanobacteria constitute a rich source of biologically active and structurally diverse compounds. The pharmacological potential of these compounds resides among others in their ability to control the proliferation and growth of cancer cell lines and potent disease-causing microbial agents. Despite recent scientific advances, the way these compounds interact with the body’s molecular structure are still unclear and science still has to discover how the cyanobacterial metabolites interact with cell structures and how cells react to them. In this project, we will study yet unexamined cyanobacterial metabolites, especially the compounds which act as chemical ligands for microRNA (miRNA) -binding sites, making them promising regulators (inhibitors) of gene networks that are involved in various diseases. We will first develop a stable cell line that constitutively expresses a unique miRNA reporter system. Then, we will conduct a screen on chemical compounds discovered in Baltic cyanobacteria to identify small molecules with inhibitory activity and specificity to MIR92b-3p, which has a significant impact on liver cell behavior in humans. We assume that a successful MIR92b-3p inhibitor will bind to the precursors of MIR92b-3p miRNA, disabling the action of either of the two processing enzymes involved in the biogenesis of any miRNA in a cell (Drosha or Dicer), thus affecting the MIR92b function. The discoveries made with these inhibitory chemical molecules could provide insight into the role of the MIR92 pathway in liver diseases and cancer, and possibly, if promising results appear, they may facilitate a strategy for treating some human diseases in the future.
Źródło:
Environmental Biotechnology; 2018, 14, 1; 1-4
1734-4964
Pojawia się w:
Environmental Biotechnology
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Design of small molecule inhibitors of type III secretion system ATPase EscN from enteropathogenic Escherichia coli
Autorzy:
Bzdzion, Lukasz
Krezel, Hanna
Wrzeszcz, Karol
Grzegorek, Irmina
Nowinska, Katarzyna
Chodaczek, Grzegorz
Swietnicki, Wieslaw
Powiązania:
https://bibliotekanauki.pl/articles/1038684.pdf
Data publikacji:
2017
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
Escherichia coli (E. coli)
type III secretion system (T3SS)
enzyme inhibitor
small molecule
Opis:
Enteropathogenic E. coli (EPEC) is a human pathogen using type III secretion system for delivery of proteins directly into the human host. The system contains a single ATPase, EscN, which is essential for uncoupling of proteins from their complexes with chaperones before the delivery. The structure of EscN ATPase (PDB code: 2obm) was used to screen computationally for small molecule inhibitors blocking its active site. Two lead candidates were examined but only one, Compound 54, was selected for further optimization. After extended QSAR optimization, two derivatives were found to be competitive inhibitors of EscN capable of blocking ATPase activity with a Ki below 50 µM. One candidate, WEN05-03, with a Ki=16±2 µM, was also minimally toxic to mammalian cells as determined by other assays. In the cell infection model of HeLa cells with EPEC, Compound WEN05-03 completely blocked actin cluster formation at 100 µM concentration, when analyzed by confocal microscopy. The second best inhibitor of EscN ATPase activity was WEN04-34 with a Ki=46±2 µM. However, the compound was highly toxic to the BALB/3T3 cell line. In summary, the work identifies a compound blocking bacterial ATPase in its active site without causing cellular toxicity to the host cells. It is the first report showing feasibility of using bacterial virulence system ATPase as a target for safe, non-toxic compounds and offering a proof-of-concept for non-antibiotic alternatives.
Źródło:
Acta Biochimica Polonica; 2017, 64, 1; 49-63
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
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