Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Molecular investigation of artificial and natural sweeteners as potential anti-inflammatory agents
Δημιουργός/Συγγραφέας:	Chontzopoulou, Eleni Papaemmanouil, Christina D Chatziathanasiadou, Maria V Kolokouris, Dimitrios Kiriakidi, Sofia Konstantinidi, Athina Gerogianni, Ioanna Tselios, Theodore Kostakis, Ioannis K [EL] Χρυσίνα, Ευαγγελία Δ.[EN] Chrysina, Evangelia D. Hadjipavlou-Litina, Dimitra [EL] Τζέλη, Δήμητρα[EN] Tzeli, Demeter Tzakos, Andreas G [EL] Μαυρομούστακος, Θωμάς[EN] Mavromoustakos, Thomas
Εκδότης:	Taylor and Francis
Ημερομηνία:	2022
Γλώσσα:	Αγγλικά
ISSN:	0739-1102 1538-0254
DOI:	10.1080/07391102.2021.1973565
Άλλο:	34499023
Περίληψη:	Repurposing existing drugs, as well as natural and artificial sweeteners for novel therapeutic indications could speed up the drug discovery process since numerous associated risks and costs for drug development can be surpassed. In this study, natural and artificial sweeteners have been evaluated by in silico and experimental studies for their potency to inhibit lipoxygenase enzyme, an enzyme participating in the inflammation pathway. A variety of different methods pinpointed that aspartame inhibits the lipoxygenase isoform 1 (LOX-1). In particular, "LOX-aspartame" complex, that was predicted by docking studies, was further evaluated by Molecular Dynamics (MD) simulations in order to assess the stability of the complex. The binding energy of the complex has been calculated after MD simulations using Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) method. Furthermore, Quantum Mechanics/Molecular Mechanics (QM/MM) calculations have been applied for geometry optimization of the "enzyme-ligand" complex. After having fully characterized the "LOX-aspartame" complex in silico, followed in vitro biological assays confirmed that aspartame inhibits LOX-1 (IC50=50 ± 3.0 μΜ) and blocks its biological response. The atomic details of aspartame's interaction profile with LOX-1 were revealed through Saturation Transfer Difference (STD) NMR (Nuclear Magnetic Resonance). Finally, aspartame was also tested with Molecular Docking and Molecular Dynamics studies for its potent binding to a number of different LOX isoforms of many organisms, including human. The in silico methods indicated that aspartame could serve as a novel starting point for drug design against LOX enzyme. Communicated by Ramaswamy H. Sarma.
Τίτλος πηγής δημοσίευσης:	Journal of biomolecular structure & dynamics
Τόμος/Κεφάλαιο:	40
Τεύχος:	23
Σελίδες:	12608-12620
Θεματική Κατηγορία:	[EL] Χημική Βιολογία[EN] Chemical Biology [EL] Ατομική φυσική (συμπ. μοριακή φυσική, σχετικότητα, κβαντική θεωρία και φυσική στερεάς κατάστασης)[EN] Atomic physics (Incl. molecular physics, relativity, quantum theory, and solid state physics) [EL] Φασματοσκοπία[EN] Spectroscopy [EL] Δομική Βιολογία[EN] Structural Biology [EL] Φαρμακευτική χημεία[EN] Pharmaceutical chemistry
Λέξεις-Κλειδιά:	Aspartame STD NMR In vitro assays lipoxygenase Molecular dynamics Humans Molecular Docking Simulation Molecular Dynamics Simulation Anti-Inflammatory Agents Lipoxygenases Scavenger Receptors, Class E Sweetening Agents Aspartame
Κάτοχος πνευματικών δικαιωμάτων:	Copyright © 2021 Informa UK Limited, trading as Taylor & Francis Group
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://doi.org/10.1080/07391102.2021.1973565
Ηλεκτρονική διεύθυνση περιοδικού (link) :	https://www.tandfonline.com/journals/tbsd20
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο