Selectivity of spermine homologs on tripler DNA stabilization

We synthesized seven homologs of spermine (H2N(CH2)(3)NH(CH2)(n)NH(CH2)(3)N H2, where n = 2-9: n = 4 for spermine) and studied their effects on melting temperature (T-m), conformation, and precipitation of poly(dA).2poly(dT), The tripler DNA melting temperature, T-m1 was 34.4 degrees C in the presenc e of 150 mM KCl, Addition of spermine homologs increased T-m1 in a concentr ation-dependent and structure-dependent manner, with 3-6-3 (n = 6) exerting optimal stabilization, The dT(m1)/dlog[polyamine] values were 9-24 for the se compounds, The duplex melting temperature, T-m2 was insensitive to homol og concentration and structure, suggesting their ability to stabilize tripl er DNA without altering the stability of the underlying duplex, Circular di chroism spectral studies revealed psi-DNA formation in a concentration-depe ndent and structure-dependent manner. Phase diagrams were constructed showi ng the critical ionic/polyamine concentrations stabilizing different struct ures. These compounds also exerted structural specificity effects on precip itating tripler DNA, These data provide new insights into the ionic/structu ral determinants affecting tripler DNA stability and indicate that 3-6-3 is an excellent ligand to stabilize poly(dA).2poly(dT) tripler DNA under phys iologic ionic conditions for antigene therapeutics.