Unit:
Κατεύθυνση Οργανική Σύνθεση και Εφαρμογές της στη Χημική ΒιομηχανίαLibrary of the School of Science
Author:
Minadakis Michail-Panagiotis
Supervisors info:
Αθανάσιος Γκιμήσης, Καθηγητής, Τμήμα Χημείας, ΕΚΠΑ
Original Title:
Σύνθεση και Μελέτη Μοριακών Στροφέων, Ιχνηθετών του Καταλυτικού Κέντρου της Φωσφορυλάσης του Γλυκογόνου
Translated title:
Synthesis and Study of Molecular Rotors, Probes of the Catalytic Center of Glycogen Phosphorylase
Summary:
The field of molecular imaging deals with the detection of specific molecular targets and the monitoring of biological processes in cells, tissues and vital organs in a non-invasive manner. Collection of molecular information requires the use of probes which exhibit high selectivity for the regions of interest. Molecular rotors are a family of synthetic fluorescent compounds which undergo an intramolecular twist process as a result of charge transfer after photoexcitation. This class of molecules bears an electron donating and an electron accepting group linked through a π-conjugate system, that have the ability to rotate relative to each other. Glycogen phosphorylase (GP) is one of the most important regulatory enzymes that control glucose homeostasis and glycogen metabolism, playing a catalytic role in the breakdown of glycogen, a major energy source stored in the body. Inhibition of GP is a promising area in the treatment of type II diabetes.
In the context of this research work, two new GP inhibitors (RotA and RotB), which belong to the molecular rotor family, were designed and synthesized. A synthetic protocol was developed and, for RotA, the inhibition constant was determined and the binding to the catalytic center of GP was confirmed by X-ray crystallography of the enzyme : inhibitor complex. Spectroscopic studies have shown that this new inhibitor exhibits molecular rotor properties which are expressed by an increase in fluorescence intensity after clustering in the closed catalytic center of the enzyme. Cellular experiments have shown that RotA can be used as a molecular marker of glycogen phosphorylase in a cellular environment. Overall, this is a novel tool that can allow an in-depth study of glycogen phosphorylase activity both in vitro and in vivo.
Main subject category:
Science
Keywords:
Organic Synthesis, RMGPb Inhibitors, Spectroscopic Study, Molecular Rotors, Biological Probes
Number of references:
225
