Comb-type copolymer: Stabilization of triplex DNA and possible application in antigene strategy

摘要: By employing a reductive amination reaction between the ϵ-amino groups of poly(L-lysine) (PLL) and ends hydrophilic dextran (Dex) side chain, we have prepared different comb-type copolymers which varied in degree grafting length Dex chains. The resulting copolymers, poly-(L-lysine)-graft-dextran (PLL-g-Dex), were tested for their ability to stabilize triplex DNA vitro under physiologically relevant conditions. Thermal denaturation (UV–Tm) circular dichroism experiments revealed that graft copolymer with higher long chains significantly increased thermal stability structure poly(dA)·2poly(dT) by more than 50 °C without affecting transition single-stranded or native DNA. Of importance is when formation involving 30-mer target duplex from rat α1 (I) collagen promoter was analyzed an electrophoretic mobility shift assay, also remarkably diminished potassium inhibition purine motif up 200 mM as well pH-dependence pyrimidine formation. Moreover triplex-stabilizing efficiency other oligocations like spermine spermidine. We suggest molecular design consisting various types polycation backbones (e.g., PLL) grafted Dex) novel strategy create efficient stabilizers will certainly shed light on possible vivo application antigene strategy.