E-Locus - Institutional Repository of the University of Crete

Home Collections Type of Work Post-graduate theses

Post-graduate theses

Current Record: 7 of 6624

[Add to Basket]

Identifier

000466050

Title

Ενώσεις "Μοριακής-Εγγύτητας" ως θεραπευτικό εργαλείο στον σχεδιασμό και ανάπτυξη βιοδραστικών μορίων. Η περίπτωση της πρωτεϊνικής αλληλεπίδρασης 14-3-3σ/ERα

Alternative Title

“Proximity-Induced” compounds as a therapeutic tool for the design and development of bioactive molecules. The case of the protein-protein interactions 14-3-3σ/ERα

Author

Ζιγγιρίδης, Μάριος Β.

Thesis advisor

Νεοχωρίτης, Κωνσταντίνος

Reviewer

Βασιλικογιαννάκης, Γεώργιος
Παυλίδης, Ιωάννης

Abstract

The present master thesis is divided into two subsections (chapters), the main focus of which is the development of “proximity-induced” compounds (based on covalent interactions) as a therapeutic tool for the design and development of bioactive molecules. Particular emphasis has been placed in the chemistry of molecular glues (MGs) for the development of new similar compounds. More specifically: In Chapter 1, compounds were developed via multicomponent reactions (MCRs) to stabilize the protein-protein interactions (PPIs) between 14-3-3σ protein and estrogen receptor alpha (ERα). Biological analysis of these compounds was performed with mass spectrometry (MS) and with Time-Resolved FRET (TR-FRET) in order to find their biological activity on the selected target. Co-crystallization of some compounds with the 14-3-3σ/ERα complex was also performed. In Chapter 2, the synthesis of tetrazole and indole derivatives possessing a warhead was carried out. The purpose of this synthesis was to test their biological activity on different targets for possible finding of new covalent inhibitors.

Language

Greek

Subject

Co-crystallization

Covalent inhibitors

ERα

Mass spectrometry

Molecular glues

Multicomponent reactions (MCRs)

PPIs

TR-FRET

Warhead