Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	The architecture of hydrogen and sulfur σ-hole interactions explain differences in the inhibitory potency of C-β-d-glucopyranosyl thiazoles, imidazoles and an N-β-d glucopyranosyl tetrazole for human liver glycogen phosphorylase and offer new insights to structure-based design
Δημιουργός/Συγγραφέας:	Kyriakis, Efthimios Karra, Aikaterini G Papaioannou, Olga Solovou, Theodora Skamnaki, Vassiliki T Liggri, Panagiota G V [EL] Ζωγράφος, Σπύρος Ε.[EN] Zographos, Spyros E. Szennyes, Eszter Bokor, Éva Kun, Sándor Psarra, Anna-Maria G Somsák, László Leonidas, Demetres D
Εκδότης:	Elsevier
Ημερομηνία:	2020-01-01
Γλώσσα:	Αγγλικά
ISSN:	09680896
DOI:	10.1016/j.bmc.2019.115196
Άλλο:	31767404
Περίληψη:	C-Glucopyranosyl imidazoles, thiazoles, and an N-glucopyranosyl tetrazole were assessed in vitro and ex vivo for their inhibitory efficiency against isoforms of glycogen phosphorylase (GP; a validated pharmacological target for the development of anti-hyperglycaemic agents). Imidazoles proved to be more potent inhibitors than the corresponding thiazoles or the tetrazole. The most potent derivative has a 2-naphthyl substituent, a Ki value of 3.2 µM for hepatic glycogen phosphorylase, displaying also 60% inhibition of GP activity in HepG2 cells, compared to control vehicle treated cells, at 100 μM. X-Ray crystallography studies of the protein - inhibitor complexes revealed the importance of the architecture of inhibitor associated hydrogen bonds or sulfur σ-hole bond interactions to Asn284 OD1, offering new insights to structure-based design efforts. Moreover, while the 2-glucopyranosyl-tetrazole seems to bind differently from the corresponding 1,2,3-triazole compound, the two inhibitors are equipotent.
Τίτλος πηγής δημοσίευσης:	Bioorganic & medicinal chemistry
Τόμος/Κεφάλαιο:	28
Τεύχος:	1
Σελίδες:	115196
Θεματική Κατηγορία:	[EL] Χημική Βιολογία[EN] Chemical Biology [EL] Κυτταρολογία[EN] Cytology [EL] Βιοχημεία[EN] Biochemistry [EL] Δομική Βιολογία[EN] Structural Biology
Λέξεις-Κλειδιά:	Crystallography, X-Ray Dose-Response Relationship, Drug Enzyme Inhibitors Glycogen Phosphorylase, Liver Form Hep G2 Cells Humans Hydrogen Imidazoles Models, Molecular Molecular Structure Structure-Activity Relationship Sulfur Tetrazoles Thiazoles Drug Design
Κάτοχος πνευματικών δικαιωμάτων:	Copyright © 2019 Elsevier Ltd. All rights reserved
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://www.sciencedirect.com/science/article/abs/pii/S0968089619314804?via%3Dihub
Ηλεκτρονική διεύθυνση περιοδικού (link) :	https://www.sciencedirect.com/journal/bioorganic-and-medicinal-chemistry
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο