Κατεύθυνση Οργανική Σύνθεση και Εφαρμογές της στη Χημική Βιομηχανία
Library of the School of Science

2023-03-17

2023

Selyavo Anastasiya

Γκιμήσης Αθανάσιος, Καθηγητής, Τμήμα Χημείας, ΕΚΠΑ
Γεωργιάδης Δημήτρης, Καθηγητής, Τμήμα Χημείας, ΕΚΠΑ
Βικτωρία Μαγκριώτη, Αναπληρώτρια Καθηγήτρια, Τμήμα Χημείας, ΕΚΠΑ

Σύνθεση καρβοκυκλικών αναλόγων της οξειδωτικής βλάβης του DNA, 8-οξο-2’-δεοξυγουανοσίνης, με σκοπό τη μελέτη του κυτταρικού μηχανισμού επιδιόρθωσης

Greek

Σύνθεση καρβοκυκλικών αναλόγων της οξειδωτικής βλάβης του DNA, 8-οξο-2’-δεοξυγουανοσίνης, με σκοπό τη μελέτη του κυτταρικού μηχανισμού επιδιόρθωσης

Oxidatively induced DNA damage is the result of the imbalance between the production of reactive oxygen and nitrogen species (ROS and NOS) and other endogenous or exogenous oxidants and the antioxidant defenses in our body. The strong disturbance of this balance leads to the phenomenon of oxidative stress which is the source of many diseases, such as inflammation and cancer. However, there are several cellular mechanisms that repair these DNA lesions. Two of the most important are the NER (Nucleotide Excision Repair) and BER (Base Excision Repair) mechanisms. In order to inhibit the BER mechanism and to exclusively study the NER mechanism in biological systems, it is necessary to synthesize carbocyclic analogues of nucleotide base lesions, which lack a glycosidic bond and therefore cannot be repaired by the BER mechanism. The aim of this Master's thesis was to synthesize carbocyclic analogues of the well-known and well-studied oxidative DNA lesion, 8-oxo-2-deoxyguanosine (8-oxodGuo). Two independent approaches were followed. In the first approach, an attempt was made to chemically modify a commercially available carbocyclic derivative of guanosine, namely entecavir, a well-known anti-hepatitis B drug. In the second and successful approach, a de novo synthesis of c-8-oxodGuo was performed, with the commercially available and chiral Vince lactam as starting material. The final aim of the present work was the synthesis of the corresponding phosphoramidite of c-8-oxodGuo, with the purpose of introducing it into synthetic oligonucleotides necessary for a biological study of the lesion’s repair by the NER mechanism by a collaborating laboratory at Friedrich Schiller University (Jena, Germany).

Science

Carbocyclic analogues of oxidative DNA lesions, de novo synthesis, Nucleotide Excision Repair mechanism, organic Synthesis, oxidatively induced DNA lesions, 8-oxo-2’-deoxyguanosine.

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File access is restricted until 2026-03-17.

https://pergamos.lib.uoa.gr/uoa/dl/object/3301203