Κατεύθυνση Οργανική Χημεία
Library of the School of Science

2016-10-11

2016

Τσικούρης Περικλής

Αθανάσιος Γκιμήσης Αναπλ. Καθηγητής

Σύνθεση τροποποιημένων πουρινών για βιολογικές και τεχνολογικές εφαρμογές

Greek

Synthesis of modified purine for biological and technological applications

Purine and more particularly 2΄-deoxypurines nucleosides, 2΄-deoxyadenosine and
2΄-deoxyguanosine, are two of the four bases that structure DNA. Those with
modified analogs have shown interest in biological terms, as they have found
widespread use as anti-cancer, antibiotic and antiviral drugs, while in recent
years are beginning to find applications as nanomaterials, such as drug
delivery systems. Modified analogues of 2-deoxypurine are also generated during
normal metabolic processes and against oxidative damage of DNA. The (5΄R) and
(5΄S)-5΄-8-cyclo-2΄-deoxyadenosine and the 7,8-dihydro-8-oxo-2-deoxyguanosine
are some of the products of oxidative damage of DNA. Previous investigations
have shown that the isomer (5΄S) in the DNA blocked DNA synthesis and the
activity of the exonuclease of DNA, while is less efficiently repaired by the
"nucleotide excision repair" mechanism (NER). As the substrates of DNA β-
polymerase are the corresponding 5΄-deoxynucleoside triphosphates, the question
raised in this thesis was whether these isomers have potential cytotoxic
effect and we set as synthetic targets the synthesis of (5΄R) and (5΄S)-5΄-
8-cyclo-2΄-deoxyadenosine. Moreover, in this thesis a second and related
synthetic target was set and completed. It is known that the guanosine is able
to self-assemble into supramolecular structures, G-quadruplexes, which form
nanostructures with interesting applications. Specifically lipophilic guanosine
analogs have the advantage to better self-assemble and form G-quadruplexes in
organic solvents. For this purpose, by modifying the of 3΄- and 5΄-OH sugar we
synthesized lipophilic O3΄-O5΄-di(decanoyl)-2'-deoxyguanosine and modified C-8
of the base creating O3΄,O5΄-di(decanoyl)-7,8-dihydro-8-oxo-2΄-deoxyguanosine
useful for investigating the self-assembly of this modified analog in
G-quadruplexes and for determining possible advantages in nano-technology
applications.

Modified analogues purines, DNA damage, Anti-cancer drugs, Nanomaterials, G-quadruplexes

Yes

1-11

Yes

194

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https://pergamos.lib.uoa.gr/uoa/dl/object/1320121