Synthesis of the Polycation Thymidyl DNG, Its Fidelity in Binding Polyanionic DNA/RNA, and the Stability and Nature of the Hybrid Complexes

摘要

We show in these preliminary investigations that the attractive forces between negatively charged DNA or RNA and positively charged DNG contribute significantly to the stability of heteroduplex and heterotriplex structures formed between these species. The differing influence of increase in ionic strength on the stability of duplex and triplex structures composed of DNA and/or RNA, as compared to such structures composed of DNG in combination with DNA or RNA, supports the importance of charge attraction and repulsion in determining stability of triplex and duplex structures. An increase in ionic strength shields electrostatic interactions, hence, decreasing the force between positive and negative charges. The repulsion between negative charges found on opposite strands of DNA and RNA duplex and triplex structures diminishes with increasing μ such that stability (T_m) increases with increasing μ. In the case of structures of DNG with DNA or RNA, the attractive forces between positive DNG and negative nucleic acid increase with decreasing μ. Thus, DNG duplex and triplex structures with DNA or RNA are much more stable at physiological ionic strength than the corresponding structures with DNA and RNA as the sole components. Regardless of the uniquely tight binding of DNG to DNA or RNA, there is a yet to be completely defined fidelity of base pair recognition. The thymine of the DNG pentamer 1 recognizes adenine but not guanine or cytosine. These features encourage us toward further characterization of DNG and its RNA analog RNG as putative antisense/antigene agents.