The effect of backbone structure on polycation comb-type copolymer/DNA interactions and the molecular assembly of DNA

A series of comb-type copolymers comprised of various polycation backbones and dextran (Dex) side chains were prepared to study the DNA/copolymer interaction. While the cationic copolymers with a lower degree of dextran grafts maintained an ability to condense DNA molecules into a globule form those with a higher degree of dextran grafting interacted with DNA without inducing DNA condensation. The structural differences in cationic backbones diversely influenced DNA hybridization as evaluated by circular dichroism (CD) spectrometry and UV-melting analyses. The copolymer having a polyallylamine (PAA) backbone induced B→A-type transformation of DNA duplex, whereas the copolymers having either α-poly(l-lysine) (αPLL) or ε-poly(l-lysine) (εPLL) backbone induced B→C-type transformation. The PAA copolymer is the first example of the artificial polymer that induces B→A-type transformation under physiologically relevant condition. UV-melting analyses of DNA strands indicated that the αPLL copolymers showed the highest stabilization efficacy toward poly(dA)·poly(dT) duplex and poly(dA)·2poly(dT) triplex without affecting reversibility of inter DNA association. Melting temperatures (Tm) of the triplex increased from 38°C to 99°C by the addition of the αPLL copolymer with an appropriate grafting degree. While the PAA copolymers had higher density of cationic groups along the backbone than αPLL copolymers, these copolymers moderately increased Tm of the DNA triplex. The PAA copolymer caused considerable hysteresis in thermal melting/reassociation processes. Note that the εPLL copolymers increased Tm of the DNA triplex and not the duplex, suggesting their potential as a triplex selective stabilizer. Chemical structures of the cationic backbones of the copolymers were characteristically affected on the copolymer/DNA interaction even if their backbones were surrounded by abundant side chains (>65 wt%) of dextran. The study suggested that tailor-made design of “functional polycounterion” is a strategy to engineer molecular assembling of DNA.