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

2024-02-28

2024

Chatzigiannoglou Paraskevas

Αθανάσιος Γκιμήσης, Καθηγητής, Τμήμα Χημείας, ΕΚΠΑ

Σύνθεση Ισοτοπικά Επισημασμένης Υδαντοΐνης, και Μελέτες Σύνθεσης Σπειροϊμινοϋδαντοΐνης, Γνωστών Προϊόντων Οξειδωτικά Επαγώμενης Βλάβης στο DNA

Greek

Synthesis of Isotope-Labelled Hydantoin, and Synthesis Studies of Spiroiminohydantoin, Known Products of Oxidatively Induced DNA Lesions

Oxidatively produced DNA lesions are damages or alterations that occur on DNA bases. These damages may result from either endogenous factors, such as metabolic processes within the cell, and exogenous factors, such as radiation, chemical nucleases and chemotherapy drugs. Oxidatively produced damage to DNA may affect its normal function, including replication and transcription. If not repaired, it may lead to mutations, genomic instability, or cell death.
The initial objective of this research thesis was to study the de novo synthesis of carbaspiroimino-hydantoin, a stable derivative of a four-electron oxidation product of guanine. The starting materials used were commercially available diethyl ketomalonate and Vince lactam.
The second objective was to synthesize an isotopically labelled thymidine with three deuteria at positions 3' and 5' of the 2’-deoxyribose moiety. The final task was to convert the above isotopically enriched thymidine to an isotopic analogue of N1-(2'-deoxy-β-D-ribofuranosyl)-5-hydroxy-5-methylhydantoin, an oxidatively produced lesion of thymidine. The starting compounds used were commercially available thymidine.
The synthesis of an isotopically enriched hydantoin is necessary in order to quantify this specific DNA lesion in human cells by utilizing the Isotope Dilution coupled with Mass Spectrometry Technique (IDMS).

Science

DNA, Oxidatively produced DNA lesions, Spiroiminohydantoin, 5-hydroxy-5-methylhydantoin, carbacyclic analogues, isotopically labeled analogues

Yes

16

Yes

146

219

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https://pergamos.lib.uoa.gr/uoa/dl/object/3390917