Syntéza látek ovlivňujících interakce řetězců nukleových kyselin.

Ondrej, Martin

Substances which can bind selectively to the DNA structures and modify its' functions are in the center of study of many researchers for several decades. A place of their action is the minor groove of DNA. Distamycin A, netropsin, Hoechst 33258 and many other compounds are substances with a potential to interact with DNA sequences, especially with A T base pairs rich ones. My thesis is focused on searching and synthesizing of molecules structurally and functionally similar to compounds mentioned above. In order to find the structure with required properties as well as the method for the synthesis, screening by preparation of various compounds has been made. Each synthesis was performed using various methods confirming that the methodology is not entirely uniform. Common required result of each synthesis was preparation of final compound in a water soluble salt. Many partial reactions were not always successful, but necessary for terminal synthesis of required compounds. Syntheses of four compounds were successful, which were tested by molecular biology methods for increasing the melting temperature. The performed tests have shown low activity of the prepared compounds. N,N'-(1,3-phenylenebis(methylene))bis(4- ((diaminomethylene)amino)-1-methyl-1H-pyrrole-2-carboxamide) seems to be the most...

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