Synergistic stabilization of triplex by combination of comb-type cationic copolymer and 2',4'-BNA.

Abstract

We examined the effect of the combination of the two triplex-stabilizing factors, poly(L-lysine)-graft-dextran (PLL-g-Dex) copolymer and 2'-O,4'-C-methylene bridged nucleic acid (2',4'-BNA) backbone modification of triplex-forming oligonucleotide (TFO), on the pyrimidine motif triplex formation at neutral pH, a condition where pyrimidine motif triplexes are unstable. The combination of both stabilizing factors that was the triplex involving the 2',4'-BNA TFO in the presence of the copolymer synergistically increased the thermal stability of the pyrimidine motif triplex at neutral pH. The present results certainly support the idea that the combination of the stabilizing factors can be a key method for triplex stabilization and may lead to progress in therapeutic applications of the antigene strategy in vivo.