MODULATION OF DNA TRIPLEX STABILITY THROUGH NUCLEOBASE MODIFICATIONS

Spermine conjugation at N-4 of 5-Me-dC in oligonucleotides (sp-ODNs) r educes the net negative charge and these as HG strands form triplexes with 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 t riplexes is shown to arise from improved association with duplex cause d by electrostatic interaction of polycationic spermine sidechain with anionic phosphate backbone of DNA and N3 protonation is not a pre-req uirement for triplexes constituted from sp-ODNs. The amplification of electrostatic component of interaction can be achieved by transformati on of primary amino group of polyamines to corresponding guanidinium f unctions leading to improved binding and stabilization of DNA triplexe s even at pH 7.0. %-Amino-dU ODNs are shown to be compatible as a cent ral strand in formation of triplexes in which pyrimidine would be in t he middle position of a triad.