title: The effect of backbone structure on polycation comb-type copolymer/DNA interactions and the molecular assembly of DNA.
abstract: 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 alpha-poly(l-lysine) (alpha PLL) or epsilon-poly(l-lysine) (epsilon PLL) 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 alpha PLL 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 (T(m)) of the triplex increased from 38 degrees Celsius to 99 degrees Celsius by the addition of the alpha PLL copolymer with an appropriate grafting degree. While the PAA copolymers had higher density of cationic groups along the backbone than alpha PLL copolymers, these copolymers moderately increased T(m) of the DNA triplex. The PAA copolymer caused considerable hysteresis in thermal melting/reassociation processes. Note that the PLL copolymers increased T(m) 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 (> wt%) of dextran. The study suggested that tailor-made design of "functional polycounterion" is a strategy to engineer molecular assembling of DNA.
authors.affiliation: PRESTO, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Yu-ichi
authors.initials: Y
authors.lastname: Sato
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kamiya
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Watanabe
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Akaike
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yoshikawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Maruyama
mesh_terms: D001665:Binding Sites; D015342:DNA Probes / Q000737:chemistry*; D004279:DNA, Viral / Q000138:chemical synthesis / Q000737:chemistry*; D003911:Dextrans / Q000737:chemistry*; D046911:Macromolecular Substances / Q000737:chemistry; D008968:Molecular Conformation; D009690:Nucleic Acid Conformation; D011073:Polyamines / Q000737:chemistry*; D011107:Polylysine / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D013329:Structure-Activity Relationship; D044366:Transition Temperature
chemical_list: D015342:DNA Probes; D004279:DNA, Viral; D003911:Dextrans; D046911:Macromolecular Substances; D011073:Polyamines; D011108:Polymers; D011107:Polylysine; C063994:polyallylamine