STABILIZATION OF DNA STRUCTURES THROUGH NUCLEOBASE MODIFICATIONS AND BISGUANIDIUM POLYAMINES

Spermine conjugation at N-4 of 5-Me-dC in oligonucleotides (sp-ODNs)re duces the net negative charge and these as HG strands form triplexes w ith foremost stability at neutral pH (7.3), in contrast to unmodified ODNs which form stable triplexes at pH 5.5. The stability of sp-ODN tr iplexes is shown to arise from improved association with duplex caused by electrostatic interaction of polycationic spermine sidechain with anionic phosphate backbone of DNA and N3 protonation is not a prerequi rement for triplexes constituted from sp-ODNs. The amplification of el ectrostatic component of interaction can be achieved by transformation of primary amino group of polyamines to corresponding guanidinium fun ctions leading to improved binding and stabilization of DNA triplexes even at pH 7.0. 5-Amino-dU ODNs are shown to be compatible as a centra l strand in formation of triplexes in which pyrimidine would be in the middle position of a triad.