| Abstract |
The aim of this thesis is the synthesis of artificial RNA nucleases. Nucleases are enzymes that induce cleavage of nucleic acids. The synthesis of artificial nucleases is essential due to possible cleavage of RNA tumor virus molecules, while at the same time the genetic material remains unaffected, due to their great selectivity .In the literature it has been proposed that hydroxamic acids show nucleosidic activity in the presence of lanthanide ions. It has also been shown that porphyrins intercalate with double stranded regions of RNA. Due to the above findings we synthesized cationic porphyrin derivatives substituted with groups.of hydroxamic acid. More specifically the following molecules were synthesized: MeC4pMH, MeC4pCISH, MeC4p TRAH, Me C4 TRIH, Me C4 pTERTH. The first three porphyrins were used in further studies because there were the only ones soluble in water. In addition, we studied the interaction of the above porphyrins with RNA molecules using UV-Vis spectroscopy. Titration studies were preformed and the results showed that MeC4pMH intercalated strongly with RNA molecules, MeC4pCISH weaker and MeC4pTRAH did not show any intercalation due to stereochemical barriers. Following, biochemical studies were performed in order to investigate the possible action of porphyrins as artificial nuleases in the presence of lanthanide ions. More specifically, with the use of electrophoreses we obtained 100 % nucleosidic activity of MeC4pMH, in the absence of lanthanide ions. Porphyrin MeC4pCISH also showed nucleosidic activity that was reinforced by the presence of Lu+3 ions, while MeC4p TRAH did not show any significant nucleosidic activity. Finally, from the findings of this thesis it can be concluded that the first two synthesized porphyrins (MeC4pMH , MeC4pCISH ) showed nucleosidic activity. We also concluded that in order for a porphyrin to appear nucleosidic activity it is necessary its intercalation with the molecule of RNA. The intercalation depends on the degree of substitution and on stereochemistry of the porhyrin molecules.
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Σύνθεση κατιονικών πορφυρινών και μελέτη της νουκλεοσιδικής τους δράσης σε μόρια RNA
