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Identifier	000443848
Title	Ανάπτυξη χιμαιρικών μορίων για πιθανές θεραπευτικές εφαρμογές κατά της COVID-19
Alternative Title	Design and analysis of chimeric molecules with potential therapeutic applications against COVID-19
Author	Λιούτα, Κυριακή Μαρία Α.
Thesis advisor	Κοκκινίδης, Μιχαήλ
Reviewer	Αθανασάκη, Ειρήνη Βόντας, Ιωάννης
Abstract	In the present work, we are developing a templating technology to fuse different protein epitopes, from native proteins, into 4 a-helical bundles creating new chimeric protein. This procedure involves a process called templating where two protein domains of interest are inserted into a parallel two-stranded a-helical coiled-coil, which forces their interaction. Due to their homotetrameric, antiparallel conformation, but also the stability of their structure, the 4 αhelical bundles are ideal scaffolds. In the present work, two heat-resistant mutants of Rop (Repressor of Primer), RM6 and its reverse sequence, the rRM6 protein, are proposed as protein templates. As part of the work, two chimeric proteins were constructed, A11/rRM6/M8 and A1/RM6/RBM. In the first case, the two meganuclease I-CreI mutants, A11 and M8, were used as functional units. This construct aims to create heterodimers of I-CreI, preventing the homodimerization of the mutants, in order to obtain the desired new specificities. The organization of the chimeric protein into larger fibrous structures, formed during its purification procedure, gives even more perspectives to this project. In the second case a chimeric protein was designed using the RM6 scaffold, as functional groups were selected, the RBM motif of the SARS-COV-2 spike glycoprotein and the α1-helix of the human ACE2 receptor. According to the Molecular Dynamics simulations, performed of the chimeric protein, a loop (L1) of the RBM motif, seem to be stabilized by the α1-helix, through their interaction. This information could be useful in the design of peptide (protein) vaccines. Finally, a purification protocol of this chimeric protein is proposed, utilizing the SUMO3 protein.
Language	Greek, English
Subject	Chimeric protein
	Χιμαιρικά μόρια
Issue date	2021-11-26
Collection	School/Department--School of Sciences and Engineering--Department of Biology--Post-graduate theses
	Type of Work--Post-graduate theses
Permanent Link	https://elocus.lib.uoc.gr//dlib/1/f/e/metadata-dlib-1637658574-115898-20650.tkl
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