Synthesis and investigation of PNA:DNA complexes containing novel aromatic residues.

摘要

The investigation of PNA•DNA complexes containing novel aromatic residues was performed. The first part of this work involved the stereoselective syntheses of aryl-C-nucleosides using silyl-protected deoxyribonolactones as starting materials. For some of the compounds produced, this route is superior to the existing methodology. The second part of this study involved the generation of novel PNA (peptide nucleic acid) monomers bearing a variety of substituted arene moieties in the place of the nucleobases. Finally, these monomers were incorporated into synthetic PNA oligomers. Hybridization of these oligomers with complementary DNAs and evaluation of the thermodynamic stabilities of the resulting duplexes provided data for an examination of the role of arene electron demand on stacking with nucleic acids and for the development of potential universal bases. The results of the former suggest that dipole-induced dipole interactions are more important in nucleic acid base stacking than other potential interactions. In the latter study, it was found that the 4-nitrophenyl residue was the best potential universal base in terms of its ability to pair equally well with any of the four natural nucleobases without much destabilization of the duplexes. The 3-nitrophenyl and 3-pyridyl residues were somewhat less promising, while the other isomeric nitrophenyl and pyridyl residues were poor universal residues.