Investigation of the stabilities of PNA-DNA and DNA-DNA complexes containing novel aromatic residues

The investigation of the stabilities of PNA·DNA and DNA·DNA complexes containing novel aromatic residues was performed. The first part of this work involved the generation of novel PNA monomers bearing a variety of substituted arene moieties in the place of the nucleobases. These monomers were incorporated into synthetic PNA pentadecamers. Hybridization of these oligomers with complementary DNAs and evaluation of the thermodynamic stabilities of the resulting duplexes provided data for an examination of the physical origins of base stacking. The results show a strong dependence on dipole-induced dipole interactions and little contribution of other potential interactions.; In the second part of this study, a series of substituted aromatic C-nucleosides were synthesized and incorporated into DNA oligomers, which have the same sequence as the PNAs. These DNAs were hybridized with complementary DNAs, and the thermal denaturation experiments provided the thermodynamic data for the duplex formation. As before with PNA-DNA duplexes, analysis of the relationship between the duplex stabilities and the physical properties of the novel residues indicated that the same interactions, dipole-induced dipole interactions, are important in DNA-DNA base stacking. Solvophobicity and van der Waals dispersion forces appear to be relatively unimportant.; Finally, the successful synthesis of a novel class of nucleosides possessing a C1'-carboxamide linkage between the sugar and an aryl moiety is described. In this way, a variety of arenes were conjugated to deoxyribose. These monomers were incorporated into single-stranded DNAs with high coupling yields, and these oligonucleotides were hybridized to complementary DNAs to form double-helical complexes. Thermal denaturation studies of the DNA duplexes revealed that the incorporation of such residues into these complexes is destabilizing. However, the bulged arrangement of the carboxamide residues (especially for the fluorescent anthraquione residue) is only slightly destabilized. These results suggest that this motif may be well suited for labeling studies.