dc.creator | Chatzileontiadou D.S.M., Tsika A.C., Diamantopoulou Z., Delbé J., Badet J., Courty J., Skamnaki V.T., Parmenopoulou V., Komiotis D., Hayes J.M., Spyroulias G.A., Leonidas D.D. | en |
dc.date.accessioned | 2023-01-31T07:44:04Z | |
dc.date.available | 2023-01-31T07:44:04Z | |
dc.date.issued | 2018 | |
dc.identifier | 10.1002/cmdc.201700688 | |
dc.identifier.issn | 18607179 | |
dc.identifier.uri | http://hdl.handle.net/11615/72648 | |
dc.description.abstract | A member of the ribonuclease A superfamily, human angiogenin (hAng) is a potent angiogenic factor. Heteronuclear NMR spectroscopy combined with induced-fit docking revealed a dual binding mode for the most antiangiogenic compound of a series of ribofuranosyl pyrimidine nucleosides that strongly inhibit hAng's angiogenic activity in vivo. While modeling suggests the potential for simultaneous binding of the inhibitors at the active and cell-binding sites, NMR studies indicate greater affinity for the cell-binding site than for the active site. Additionally, molecular dynamics simulations at 100 ns confirmed the stability of binding at the cell-binding site with the predicted protein–ligand interactions, in excellent agreement with the NMR data. This is the first time that a nucleoside inhibitor is reported to completely inhibit the angiogenic activity of hAng in vivo by exerting dual inhibitory activity on hAng, blocking both the entrance of hAng into the cell and its ribonucleolytic activity. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim | en |
dc.language.iso | en | en |
dc.source | ChemMedChem | en |
dc.source.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85040585444&doi=10.1002%2fcmdc.201700688&partnerID=40&md5=69d2e7f451216a71eaeea6a4b7fdc2ba | |
dc.subject | angiogenin | en |
dc.subject | purine nucleotide | en |
dc.subject | pyrimidine nucleoside | en |
dc.subject | angiogenin | en |
dc.subject | pancreatic ribonuclease | en |
dc.subject | Article | en |
dc.subject | cell adhesion | en |
dc.subject | chemical structure | en |
dc.subject | computer model | en |
dc.subject | heteronuclear nuclear magnetic resonance | en |
dc.subject | human | en |
dc.subject | in vivo study | en |
dc.subject | molecular docking | en |
dc.subject | molecular dynamics | en |
dc.subject | predictive value | en |
dc.subject | priority journal | en |
dc.subject | protein interaction | en |
dc.subject | angiogenesis | en |
dc.subject | animal | en |
dc.subject | antagonists and inhibitors | en |
dc.subject | binding site | en |
dc.subject | cell line | en |
dc.subject | chemistry | en |
dc.subject | chick embryo | en |
dc.subject | chorioallantois | en |
dc.subject | computer simulation | en |
dc.subject | drug effect | en |
dc.subject | nuclear magnetic resonance | en |
dc.subject | structure activity relation | en |
dc.subject | vascularization | en |
dc.subject | Animals | en |
dc.subject | Binding Sites | en |
dc.subject | Cell Line | en |
dc.subject | Chick Embryo | en |
dc.subject | Chorioallantoic Membrane | en |
dc.subject | Computer Simulation | en |
dc.subject | Humans | en |
dc.subject | Molecular Dynamics Simulation | en |
dc.subject | Neovascularization, Physiologic | en |
dc.subject | Nuclear Magnetic Resonance, Biomolecular | en |
dc.subject | Pyrimidine Nucleosides | en |
dc.subject | Ribonuclease, Pancreatic | en |
dc.subject | Structure-Activity Relationship | en |
dc.subject | John Wiley and Sons Ltd | en |
dc.title | Evidence for Novel Action at the Cell-Binding Site of Human Angiogenin Revealed by Heteronuclear NMR Spectroscopy, in silico and in vivo Studies | en |
dc.type | journalArticle | en |