Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Discovery of the glycogen phosphorylase-modulating activity of a resveratrol glucoside by using a virtual screening protocol optimized for solvation effects
Δημιουργός/Συγγραφέας:	Mavrokefalos N. Myrianthopoulos V. Chajistamatiou A.S. [EL] Χρυσίνα, Ευαγγελία Δ.[EN] Chrysina, Evangelia D. Mikros E.
Εκδότης:	Georg Thieme Verlag
Ημερομηνία:	2015
Γλώσσα:	Αγγλικά
ISSN:	0032-0943
DOI:	10.1055/s-0035-1545910
Άλλο:	PubMed ID: 25875507
Περίληψη:	The identification of natural products that can modulate blood glucose levels is of great interest as it can possibly facilitate the utilization of mild interventions such as herbal medicine or functional foods in the treatment of chronic diseases like diabetes. One of the established drug targets for antihyperglycemic therapy is glycogen phosphorylase. To evaluate the glycogen phosphorylase inhibitory properties of an in-house compound collection consisting to a large extent of natural products, a stepwise virtual and experimental screening protocol was devised and implemented. The fact that the active site of glycogen phosphorylase is highly hydrated emphasized that a methodological aspect needed to be efficiently addressed prior to an in silico evaluation of the compound collection. The effect of water molecules on docking calculations was regarded as a key parameter in terms of virtual screening protocol optimization. Statistical analysis of 125 structures of glycogen phosphorylase and solvent mapping focusing on the active site hydration motif in combination with a retrospective screening revealed the importance of a set of 29 crystallographic water molecules for achieving high enrichment as to the discrimination between active compounds and inactive decoys. The scaling of Van der Waals radii of system atoms had an additional effect on screening performance. Having optimized the in silico protocol, a prospective evaluation of the in-house compound collection derived a set of 18 top-ranked natural products that were subsequently evaluated in vitro for their activity as glycogen phosphorylase inhibitors. Two phenolic glucosides with glycogen phosphorylase-modulating activity were identified, whereas the most potent compound affording mid-micromolar inhibition was a glucosidic derivative of resveratrol, a stilbene well-known for its wide range of biological activities. Results show the possible phytotherapeutic and nutraceutical potential of products common in the Mediterranean countries, such as red wine and Vitis products in general or green raw salads and herbal preparations, where such compounds are abundant.
Τίτλος πηγής δημοσίευσης:	Planta Medica
Τόμος/Κεφάλαιο:	81
Τεύχος:	6
Σελίδες:	507-516
Θεματική Κατηγορία:	[EL] Βιολογία (Γενικά)[EN] Biology (General) [EL] Χημεία (Γενικά)[EN] Chemistry (General)
Λέξεις-Κλειδιά:	diabetes docking-scoring glycogen phosphorylase hydration mapping solvation effects tachioside trans-resveratrol glucoside virtual screening
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
Κάτοχος πνευματικών δικαιωμάτων:	© Georg Thieme Verlag KG Stuttgart New York.
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο