Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	A glucose-based molecular rotor inhibitor of glycogen phosphorylase as a probe of cellular enzymatic function
Δημιουργός/Συγγραφέας:	Minadakis, Michail-Panagiotis Mavreas, Konstantinos F Neofytos, Dionysios D Paschou, Maria Kogkaki, Artemis Athanasiou, Varvara Mamais, Michael Veclani, Daniele Iatrou, Hermis Venturini, Alessandro [EL] Χρυσίνα, Ευαγγελία Δ.[EN] Chrysina, Evangelia D. Papazafiri, Panagiota Gimisis, Thanasis
Ημερομηνία:	2022-03-23
Γλώσσα:	Αγγλικά
DOI:	10.1039/d1ob02211c
Άλλο:	35119451
Περίληψη:	Molecular rotors belong to a family of fluorescent compounds characterized as molecular switches, where a fluorescence on/off signal signifies a change in the molecule's microenvironment. Herein, the successful synthesis and detailed study of (E)-2-cyano-3-(p-(dimethylamino)phenyl)-N-(β-D-glucopyranosyl)acrylamide (RotA), is reported. RotA was found to be a strong inhibitor of rabbit muscle glycogen phosphorylase (RMGPb), that binds at the catalytic site of the enzyme. RotA's interactions with the residues lining the catalytic site of RMGPb were determined by X-ray crystallography. Spectroscopic studies coupled with theoretical calculations proved that RotA is a molecular rotor. When bound in the catalytic channel of RMGPb, it behaved as a light switch, generating a strong fluorescence signal, allowing utilization of RotA as a probe that locates glycogen phosphorylase (GP). RotA, mono-, di- and per-acetylated derivatives, as well as nanoparticles with RotA encapsulated in polyethylene glycol-poly-L-histidine, were used in live cell fluorescence microscopy imaging to test the delivery of RotA through the plasma membrane of HepG2 and A431 cells, with the nanoparticles providing the best results. Once in the intracellular milieu, RotA exhibits remarkable colocalization with GP and significant biological effects, both in cell growth and inhibition of GP.
Τίτλος πηγής δημοσίευσης:	Organic & biomolecular chemistry
Τόμος/Κεφάλαιο:	20
Τεύχος:	12
Σελίδες:	2407–2423
Θεματική Κατηγορία:	[EL] Κρυσταλλογραφία[EN] Crystallography [EL] Φασματοσκοπία[EN] Spectroscopy [EL] Βιοχημεία[EN] Biochemistry [EL] Δομική Βιολογία[EN] Structural Biology [EL] Νανοτεχνολογία[EN] Nanotechnology
Λέξεις-Κλειδιά:	Animals Binding Sites Crystallography, X-Ray Glycogen Phosphorylase Kinetics Oligosaccharides Rabbits Enzyme Inhibitors Glucose Molecular Probes
EU Grant identifier:	MIS 5048135 MIS 5002550 653706 NSRF 2014–2020 H2020-MSCA-RISE/EU
Κάτοχος πνευματικών δικαιωμάτων:	© 2022 The Royal Society of Chemistry
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://pubs.rsc.org/en/content/articlelanding/2022/OB/D1OB02211C
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο