Differential effects of cyclopolyamines on the stability and conformation of triplex DNA

Linear polyamines are excellent promoters of tripler DNA formation, The eff ects of structural rigidization of polyamines on tripler DNA stability are not known at present. We wished to develop a series of polyamine analogs as secondary ligands for tripler DNA stabilization for antigene applications, To accomplish this goal, we synthesized cyclopolyamines by interconnecting the two amino or imino groups of linear polyamines with a -(CH2)(n)-bridge (n = 3,4,5). Melting temperature (T-m) data showed that [4,3]-spermine and [4,4]-spermine stabilized poly(dA) . 2poly(dT) triplex at > 25 mu M concen trations (T-m = 71 degrees C at 100 mu M) The dTm/dlog [polyamine] values f or these compounds were 26 and 40, respectively. [4,3]-Spermine and [4,4]-s permine also stabilized tripler DNA formed by a purine-motif tripler-formin g oligonucleotide, TG(3)TG(4)TG(4)TG(3)T with its target duplex, as determi ned by T-m, circular dichroism (CD) spectroscopy, and electrophoretic mobil ity shift assay (EMSA), In contrast, [4,4]-putrescine and [4,5]-putrescine as well as [4,5]-spermine had no tripler DNA stabilizing effect. CD spectra also showed tripler DNA aggregation and Psi-DNA formation at > 100 mu M [4 ,3]-spermine, These data demonstrate that structural rigidization of linear polyamines has a profound effect on their ability to stabilize tripler DNA and provoke conformational transitions.