Drug repurposing against fucosyltransferase-2 via docking, STD-NMR, and molecular dynamic simulation studies.

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  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science
    • Subject Terms:
      Fucosyltransferases*/metabolism ; Fucosyltransferases*/chemistry ; Drug Repositioning* ; Molecular Docking Simulation* ; Molecular Dynamics Simulation* ; Galactoside 2-alpha-L-fucosyltransferase*; Humans ; Magnetic Resonance Spectroscopy ; Enzyme Inhibitors/pharmacology ; Enzyme Inhibitors/chemistry ; Protein Binding
    • Abstract:
      Aberrant fucosylation is the hallmark of malignant cell transformation, leading to many cellular events, such as uncontrolled cell proliferation, angiogenesis, tumor cell invasion, and metastasis. This increased fucosylation is caused due to the over-expression of fucosyltransferases (FUTs) that catalyzes the transfer of the fucose (Fuc) residue from GDP-fucose (donor substrate) to various oligosaccharides, glycoproteins, and glycolipids (acceptor substrates). Hence, fucosyltransferases (FUTs) are considered as validated target for the drug discovery against on cancers. In the current study, a drug repurposing approach was deployed to identify new hits against fucosyltransferase 2 (FUT2), using computational and biophysical techniques. A library of 500 US-FDA approved drugs were screened in-silico against fucosyltransferase 2 (FUT2) donor and acceptor sites. Five drugs were predicted as hits, based on their significant docking scores (-5.8 to -8.2), and binding energies (-43 to -51.19 Kcal/mol). Furthermore, STD-NMR highlighted the epitope of these drugs in the binding site of fucosyltransferase 2 (FUT2). Simulation studies provided insights about the binding site of these drugs, and 4 of them, acarbose, ascorbic acid, ibuprofen, and enalaprilat dihydrate, were found as significant binders at the donor binding site of fucosyltransferase 2 (FUT2). Hence, the current study reports the repurposed drugs as potential hits against fucosyltransferase 2 (FUT2). These may be further studied through in-vitro and in-vivo inhibitory and mechanistic studies.
      Competing Interests: The authors have declared that no competing interests exist.
      (Copyright: © 2024 Atif et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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    • Accession Number:
      EC 2.4.1.- (Fucosyltransferases)
      EC 2.4.1.69 (Galactoside 2-alpha-L-fucosyltransferase)
      0 (Enzyme Inhibitors)
    • Publication Date:
      Date Created: 20241101 Date Completed: 20241101 Latest Revision: 20241103
    • Publication Date:
      20241104
    • Accession Number:
      PMC11530067
    • Accession Number:
      10.1371/journal.pone.0308517
    • Accession Number:
      39485776