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NMR Investigations on Oligonucleotide-Porphyrin Complexes

Interactions between DNA helices and drugs have become a focus of interest, because most of the substances that are interacting with double helices exhibit antibiotic or antitumor activity and those which interact with quadruplex DNA show telomerase inhibition activity [1, 2, 3]. However, most of the known effective drugs are not binding selectively to the nucleus of the target cells. Therefore, it is a great challenge to increase the specificity of these drugs in order to reduce their negative side effects. The aim of the study is to confirm the binding mode and obtain detailed structural information of cationic porphyrins which are bond to DNA. For combined NMR investigations model compounds have been selected to investigate the DNA-porphyrin interaction. In this study 5, 10, 15, 20-tetrakis(N-methylpyridinium-4-yl)porphyrin tetrachloride (TMPyPCl4) was chosen because it is a telomerase inhibitor and it is used for photodynamic therapy due to its high quantum yield in singlet oxygen production [4, 5]. In addition to this, it can bind to duplex DNA in three proposed binding modes: intercalation, outside surface (or groove) binding, and outside surface binding with self-stacking [6]. After preliminary investigations using circular dichroism spectroscopy, indicated that the binding mode is by intercalation, further structural investigations of the oligonucleotide d(GCGCGC)2 and its complexes with 5, 10, 15, 20-tetrakis(N-methylpyridinium-4-yl)porphyrin tetrachloride (TMPyP-Cl4) were performed by NMR spectroscopy. With these experiments the intercaIative binding mode of TMPyP-Cl4 was confirmed, and a significant change in the dihedral angles beta and epsilon of the phosphorus backbone upon TMPyP-Cl4 binding could be observed.

DNA binding; porphyrin complexes; NMR

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