DNA

Langmuir 2007, 23, 65-69

65

Spectroscopic Investigation of Cationic Comb-Type Copolymers/DNA Interaction: Interpolyelectrolyte Complex Enhancement Synchronized with DNA Hybridization† Yuichi Sato,‡ Rui Moriyama,| Sung Won Choi,| Arihiro Kano,| and Atsushi Maruyama*,‡,§,| Precursory Research for Embryonic Science and Technology (PRESTO) and Core Research for EVolutional Science and Technology (CREST), Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan, and Institute for Materials Chemistry and Engineering, Kyushu UniVersity, 6-10-1 Hakozaki, Higashi, Fukuoka 812-8581, Japan ReceiVed June 2, 2006. In Final Form: July 26, 2006 We have demonstrated that cationic comb-type copolymers consisting of a polycation backbone and abundant grafts of water-soluble polymers stabilize DNA hybrids. Furthermore, the copolymers were found to accelerate strand exchange reaction between a double-stranded DNA and its complementary single-stranded DNA. In this article, we investigated the effects of PLL-g-Dex on base pairs of a self-complementary DNA octamer, d(GGAATTCC). The soluble interpolyelectrolyte complex (IPEC) between the DNA and copolymer allowed us to characterize the complex by using spectroscopic methods under physiological ionic condition. Chemical shifts of nucleobase proton signals were not changed by PLL-g-Dex. Furthermore, the copolymer slightly changed the von’t Hoff ∆H accompanying the helix-coil transition of the octamer. These results indicated that the base pairs of the duplex DNA in the IPEC were not perturbed by the polycationic copolymer. It was obviously shown by temperature dependencies of proton and phosphorus NMR spectra that DNA/copolymer interaction was considerably enhanced in response to ds DNA formation. An increase in the density and total number of DNA negative charges upon hybrid formation likely caused the higher affinity of the copolymer with the ds form over that of the copolymer with the ss form. The IPEC formation of CCCs with DNA, however, seems highly sensitive to the coil-helix transition of the DNA.

Introduction Studies on the interaction between nucleic acids and cationic polymers, especially basic peptides as a model of nucleic acid binding protein, began in the 1960s.1-4 In the past few decades, various types of cationic polymers have been studied with the aim of transferring genetic materials into cells for biological and medical purposes.5 However, studies on the interaction between polycations and nucleic acids have been hampered by the aggregation, precipitation, and condensation (or compaction) of the resulting interpolyelectrolyte complexes (IPECs). We have been interested in cationic comb-type copolymers (CCCs) composed of small fraction (80 wt %) of water-soluble polymers.6,7 † Part of the Stimuli-Responsive Materials: Polymers, Colloids, and Multicomponent Systems special issue. * Corresponding author. E-mail: [email protected]. Phone: +81-92-642-3097. Fax: +81-92-642-4224. ‡ Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency. § Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency. | Kyushu University.

(1) Leng, M.; Felsenfeld, G. Proc. Natl. Acad. Sci. U.S.A. 1966, 56, 13251332. (2) Tsuboi, M.; Matsuo, K.; Ts’o, P. O. J. Mol. Biol. 1966, 15, 256-267. (3) Olins, D. E.; Olins, A. L.; Von Hippel, P. H. J. Mol. Biol. 1967, 24, 157-176. (4) Matsuo, K.; Mitsui, Y.; Iitaka, Y.; Tsuboi, M. J. Mol. Biol. 1968, 38, 129-132. (5) For reviews, see Lemieux, P.; Vinogradov, S. V.; Gebhart, C. L.; Guerin, N.; Paradis, G.; Nguyen, H. K.; Ochietti, B.; Suzdaltseva, Y. G.; Bartakova, E. V.; Bronich, T. K.; St-Pierre, Y.; Alakhov, V. Y.; Kabanov, A. V. J. Drug Target 2000, 8, 91-105. Hwang, S. J.; Davis, M. E. Curr. Opin. Mol. Ther. 2001, 3, 183-191. Kakizawa, Y.; Kataoka, K. AdV. Drug DeliVery ReV. 2002, 54, 203222. Thomas, M.; Klibanov, A. M. Appl. Microbiol. Biotechnol. 2003, 62, 2734. Read, M. L.; Logan, A.; Seymour, L. W. AdV. Genet. 2005, 53PA, 19-46. (6) Maruyama, A.; Katoh, M.; Ishihara, T.; Akaike, T. Bioconjugate Chem. 1997, 8, 3-6.

The copolymer forms a totally soluble IPEC in which DNA condensation is suppressed.8 We have demonstrated that the copolymer effectively stabilizes DNA hybrids,6,7,9 such as duplexes and triplexes, by reducing the counterion condensation effects accompanying hybridization processes.10 Interestingly, an increase in the association rate rather than a decrease in the dissociation rate in the hybridization process is shown to be a kinetic effect of the copolymer.11-13 Recently, we found that the copolymers considerably stimulated the strand exchange reaction (SER) between a DNA duplex and its complementary singlestranded DNA.14,15 The copolymers increase the SER rate by more than 4 orders of magnitude. DNA SER is a pivotal process in homologous recombination and repair of DNA in vivo.16-19 It is known that recombination proteins, such as RecA and Rad51, accelerate the rate of the (7) Maruyama, A.; Watanabe, H.; Ferdous, A.; Katoh, M.; Ishihara, T.; Akaike, T. Bioconjugate Chem. 1998, 9, 292-299. (8) Sato, Y.; Kim, W. J.; Saito, M.; Kano, A.; Akaike, T.; Maruyama, A. Nucleic Acids Res. Suppl. 2003, 129-130. (9) Ferdous, A.; Watanabe, H.; Akaike, T.; Maruyama, A. Nucleic Acids Res. 1998, 26, 3949-3954. (10) Maruyama, A.; Ohnishi, Y.; Watanabe, H.; Torigoe, H.; Ferdous, A.; Akaike, T. Colloids Surf., Bs 1999, 16, 273-280. (11) Torigoe, H.; Ferdous, A.; Watanabe, H.; Akaike, T.; Maruyama, A. J. Biol. Chem. 1999, 274, 6161-6167. (12) Ferdous, A.; Akaike, T.; Maruyama, A. Bioconjugate Chem. 2000, 11, 520-526. (13) Torigoe, H.; Maruyama, A. Syne′′. Am. Chem. Soc. 2005, 127, 17051710. (14) Kim, W. J.; Ishihara, T.; Akaike, T.; Maruyama, A. Chem.sEur. J. 2001, 7, 176-180. (15) Kim, W. J.; Akaike, T.; Maruyama, A. J. Am. Chem. Soc. 2002, 124, 12676-12677. (16) Shinohara, A.; Ogawa, T. Mutat. Res. 1999, 435, 13-21. (17) Shibata, T.; Nishinaka, T.; Mikawa, T.; Aihara, H.; Kurumizaka, H.; Yokoyama, S.; Ito, Y. Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 8425-8432. (18) Aguilera, A. Trends Genet. 2001, 17, 318-321. (19) Kawabata, M.; Kawabata, T.; Nishibori, M. Acta Med. Okayama 2005, 59, 1-9.

10.1021/la0615847 CCC: $37.00 © 2007 American Chemical Society Published on Web 09/15/2006

66 Langmuir, Vol. 23, No. 1, 2007

Figure 1. Self-complementary DNA octamer (a) and the chemical formula of the PLL-g-Dex copolymer (b).

exchange reaction through nucleoprotein filament formation with single-stranded (ss) and double-stranded (ds) DNAs. Nucleic acid (NA) chaperones that support the correct hybridization or folding of nucleic acids are another class of proteins that accelerate the SER of nucleic acids.20-22 The NA chaperones reduce the energy barrier accompanying the dissociation and reassociation of base pairs, catalyzing nucleic acids refolding into the thermodynamically most stable conformer from metastable ones. We consider that the activity of CCCs to stimulate SER seemingly resembles that of the NA chaperones. The retroviral nucleocapsid proteins (NCp)s are well-characterized NA chaperones.23 The NCps are small and highly basic proteins having one or two zinc-finger motifs. The NCp was revealed to decrease the melting temperature (Tm) of ds DNAs,24 indicating that NCp destabilizes base pairs to stimulate a strand-exchange reaction. It is interesting that this feature of NCp strikingly contrasts with that of CCCs because CCCs stimulate the reaction while stabilizing ds DNA. Nevertheless, there might be a possibility that CCCs locally perturb base pairs of the initial ds DNA to trigger the strandexchange reaction. To assess this possibility, we investigate the effect of CCCs on the DNA base pairs employing NMR, CD, and UV-Tm measurements. Chemical shifts of nucleobase proton signals and van’t Hoff ∆H accompanying the coil-helix transition of DNA were not significantly changed by the added CCCs, indicating that the CCCs did not influence the base-pair structures. Hence, the stimulating effect of CCCs on the strand-exchange reaction likely involves no local perturbation of the initial duplex structure. Furthermore, in the course of the study, it was obviously shown that IPEC between DNA and CCC is synchronously enhanced by the hybridization process. The interaction of CCCs with DNA seems to be highly sensitive to the coil-helix transition of DNAs. Experimental Procedure Materials. d(GGAATTCC) (Figure 1a) were HPLC-purified grade obtained from Fasmac Co. (Tokyo, Japan). The absorption coefficient (260 nm) was determined to be 5.4 × 104 M-1 cm-1 at 25 °C. The PLL-g-Dex copolymer (Figure 1b, Mn of PLL ) 14 400, Mn of Dex ) 5300, degree of substitution of Dex ) 14.4 mol %, weight fraction of Dex ) 86 wt %) was prepared by a reductive amination reaction (20) Herschlag, D. J. Biol. Chem. 1995, 270, 20871-20874. (21) Rein, A.; Henderson, L. E.; Levin, J. G. Trends Biochem. Sci. 1998, 23, 297-301. (22) Schroeder, R.; Barta, A.; Semrad, K. Nat. ReV. Mol. Cell Biol. 2004, 5, 908-919. (23) Tsuchihashi, Z.; Brown, P. O. J. Virol. 1994, 68, 5863-5870. (24) Urbaneja, M. A.; Wu, M.; Casas-Finet, J. R.; Karpel, R. L. J. Mol. Biol. 2002, 318, 749-764.

Sato et al. between poly(L-lysine) and dextran, as described in detail previously.6,7 Anhydrous betaine(N,N,N-trimethylglycine) (>98% pure) was purchased from Wako Pure Chemical Industries, Ltd. (Osaka, Japan). NMR Measurements. Samples were dissolved in a D2O solution of 100 mM NaCl and 1 mM EDTA buffered with 10 mM sodium phosphate at pD 7.5. The 1H and 31P NMR spectra were recorded with a 270 MHz JEOL JNM-EX270 spectrometer. Proton chemical shifts are referenced to internal HDO molecules (δ ) 4.65 in D2O), whereas phosphorus chemical shifts are referenced to external 85% H3PO4 molecules (δ ) 0 in D2O). UV-Tm Measurements. UV-Tm measurements were carried out with a Shimadzu UV-1600PC spectrophotometer equipped with a temperature-controlled cell holder. DNA melting profiles in a 10 mM sodium phosphate buffer (pH 7.3) containing 100 mM NaCl and 1 mM EDTA were monitored by differential absorption (A260 nm - A340 nm) to correct baseline shift. The melting midpoint was designated as Tm. CD Measurements. CD measurements were carried out in a JASCO J-700 spectropolarimeter. Each spectrum shown was the average of four scans that have been smoothed. Circular dichroism is expressed as molar ellipticity [θ] ) θ/cl, where θ is the measured ellipicity in degrees, c is the molar concentration (in repeating units of DNA or polycation), and l is the path length in the quartz cell. The CD samples were prepared in 10 mM sodium phosphate buffer (pH 7.3) containing 100 mM NaCl and 1 mM EDTA at various polymer/DNA charge ratios (N/P ) [amino group]polymer/[phosphate group]DNA).

Results and Discussion Chemical Shifts in Nonexchangeable Protons of Nucleobase. Patel and Canuel25 have studied the helix-coil transition of selfcomplementary DNA octamer d(GGAATTCC) by UV-melting and NMR measurements. They reported that significant changes in the chemical shifts of the base protons occurred in accordance with the helix-coil transition. The proton NMR study of the octamer was further explored by Broido et al.26,27 We employed the octamer to assess the effect of PLL-g-Dex on DNA base pair structures. The temperature dependences of the base proton signals in the absence or presence of an electrostatically equivalent amount (N/P ) 1) of PLL-g-Dex are shown in Figure 2. The proton NMR spectra at 35 and 45 °C, respectively, in the absence and presence of PLL-g-Dex correspond to the ds DNA state, whereas those at 75 °C correspond to the ss DNA state. The nonexchangeable proton signals of nucleobases between 7.0 and 8.5 ppm were assigned to the adenine H-2, H-8, guanine H-8, cytosine H-6, and thymine H-6 signals according to previous work by Broido et al.27 All of the signals continued to shift downfield with increasing temperature. Though the proton signals broadened in the presence of PLL-g-Dex at the lower temperature, some signals such as the H-6 proton (T5H6) of thymine at the fifth position and the H-2 proton (A4H2) of adenine at the fourth position were clearly separated from other signals. The temperature dependence of the T5H6 signal from 20 to 80 °C was monitored to trace thermal melting of the ds octamers. The melting profiles depicted from the chemical shift of T5H6 in the absence and presence of either of PLL-g-Dex or betaine are shown in Figure 3A. The values of Tm (designated as a transition midpoint) are 47 and 60 °C, respectively, in the absence and presence of the copolymer, indicating that PLL-g-Dex increased the Tm by 13 °C. Note that the chemical shifts (Figure 3A) of the protons before and after the coil-helix transition were identical to that (25) Patel, D. J.; Canuel, L. L. Eur. J. Biochem. 1979, 96, 267-276. (26) Broido, M. S.; James, T. L.; Zon, G.; Keepers, J. W. Eur. J. Biochem. 1985, 150, 117-128. (27) Broido, M. S.; Zon, G.; James, T. L. Biochem. Biophys. Res. Commun. 1984, 119, 663-670.

Cationic Comb-Type Copolymer/DNA Interaction

Langmuir, Vol. 23, No. 1, 2007 67

Figure 2. 1H NMR spectra (270 MHz) of 3.0 mM d(GGAATTCC) in the absence or presence of PLL-g-Dex (N/P ) 1) in D2O containing 100 mM NaCl and 1 mM EDTA buffered with 10 mM phosphate (pD 7.5) at various temperatures.

Figure 4. Plots of the inverse of the transition midpoint (Tm-1) against the total strand concentration for the DNA octamer in 10 mM phosphate buffer (pH 7.3) containing 100 mM NaCl and 1 mM EDTA.

Figure 3. Temperature dependence of the chemical shift (a) and differential chemical shift (b) of T5H6 proton signals of d(GGAATTCC) in the absence or presence of PLL-g-Dex (N/P ) 1).

without PLL-g-Dex and the melting profiles detected by the T5H6 proton signals are not influenced by PLL-g-Dex as seen from plots (Figure 3B) of ∆δ/∆T versus temperature. These

results strongly suggested a negligible effect of PLL-g-Dex on local base-pair structures of the ds octamers. We compared the effect of the copolymer with that of 5 M betaine, which is known to have an isostabilization effect (i.e., elimination of the base composition dependence of thermal melting28). In the presence of betaine, the chemical shift of the T5H6 proton signal in the ds state (below 40 °C) and the melting profile of the ds octamer were largely changed. Effect of PLL-g-Dex on the Thermodynamic Parameters of the Helix-Coil Transition. The transition midpoints (Tm) of the self-complementary d(GGAATTCC) duplex at 10-240 µM DNA strand concentrations (Ct) were determined by UV-melting curve measurements. Figure 4 shows semilogarithmic plots of Tm-1 values versus Ct. The linear relationships in Figure 4 provide an estimation of the enthalpy (∆H°) and entropy (∆S°) of the transition.25,29 ∆H° values of approximately -40 kcal mol-1 either in the absence or presence of PLL-g-Dex were obtained, suggesting that PLL-g-Dex did not affect hydrogen bonding and (28) Rees, W. A.; Yager, T. D.; Korte, J.; von Hippel, P. H. Biochemistry 1993, 32, 137-144. (29) Kallenbach, N. R.; Berman, H. M. Q. ReV. Biophys. 1977, 10, 138-236.

68 Langmuir, Vol. 23, No. 1, 2007

Sato et al.

Figure 5. Temperature dependence of line widths of the T5H6 resonance in the absence or presence of PLL-g-Dex (N/P ) 1).

stacking interactions of the ds octamers. However, the ∆S° values estimated in the absence and presence of PLL-g-Dex were -113 and -99 cal mol-1 K-1, respectively, implying that the copolymer stabilizes the duplex by reducing the entropic factors. The result is consistent with that of our previous study on triple-helical DNA stabilization with PLL-g-Dex.11 The copolymers stabilize DNA hybrids by reducing counterion condensation effects that are entropically unfavorable for the hybridization of nucleic acids.10 In the presence of 5 M betaine, calculated values of ∆H° and ∆S° are -53 kcal mol-1 and -154 cal mol-1 K-1, respectively. Betaine markedly influenced overall thermodynamics of the helix-coil transition. Enhanced IPEC upon DNA Double Helix Formation. As shown in Figure 2, proton signals of the DNA octamer broaden considerably at the lower temperature in the presence of PLLg-Dex, whereas slight broadening of the signals occurred at the higher temperature. The peak broadening was presumed to be due to the restricted molecular motion of the DNA by the interaction with PLL-g-Dex. The line width of the T5H6 protons with decreasing temperature was measured and is plotted against temperature in Figure 5. In the absence of the copolymer, the line width temporarily increased during the coil-helix transition process. The temporal increase in the line width is explained by the rapid dynamics of base pair association and dissociation under the transition condition.30 In the presence of PLL-g-Dex, the line width similarly began to increase with decreasing temperature to the transition temperature range and kept increasing to a temperature below the transition-temperature range. The result strongly indicated that the interaction of the octamers with PLL-g-Dex was enhanced upon DNA hybridization. To confirm the influence of the coil-helix transition on the copolymer/ DNA interaction, a parallel NMR study with the non-selfcomplementary DNA octamer in the absence and presence of an excess amount of PLL-g-Dex (N/P ) 2) was performed (Supporting Information). Although an increase in peak broadening with decreasing temperature was observed in the presence of PLL-g-Dex, the extent of the broadening was considerably smaller than that observed with the self-complementary octamer at N/P ) 1. Because PLL-g-Dex principally interacts with DNA through ionic interactions with phosphate groups of the DNA, the 31P signals of the phosphodiester backbone were also studied by 31P NMR spectroscopy. The temperature dependencies of the 31P chemical shifts in the absence or presence of PLL-g-Dex are shown in Figure 6. At 80 °C, no significant change in the 31P (30) Braunlin, W. H.; Bloomfield, V. A. Biochemistry 1991, 30, 754-758.

Figure 6. FT phosphorus NMR spectra (109.4 MHz) of 0.3 mM d(GGAATTCC) in the absence or presence of PLL-g-Dex (N/P ) 1) in D2O containing 10 mM sodium phosphate (pD7.5), 100 mM NaCl, and 1 mM EDTA at various temperatures.

signals by the copolymer was observed, suggesting a weak interaction of the copolymer with the ss octamer. At 40 °C, strong broadening of the signals in the presence of PLL-g-Dex was observed. The IPEC enhancement synchronizing with the double-helix formation was further characterized by 1H NMR of the copolymer. The -methylene proton signal of the PLL backbone in the absence or presence of the octamer was observed with varying temperature. As shown in Figure 7, the -methylene proton signal significantly broadens below 60 °C in the presence of the DNA octamers. We also observed proton signals of the dextran grafts of PLL-g-Dex. NMR signals of the dextran anomer protons did not change regardless of the existence of octamers. Interestingly, the dextran proton signal did not broaden but became sharper in the presence of the octamer at the lower temperature (Supporting Information). Whereas segmental mobility of the PLL backbone was strongly restricted upon enhanced IPEC formation with ds DNA, the dextran moieties had high mobility. This dynamic property of the dextran moieties is considered to be important for acquiring high IPEC solubility between DNA and PLL-g-Dex. Estimation of Conformational Change of the Copolymer Backbone upon IPEC Formation. Whereas the PLL homopolymer at neutral pH takes an extended coil conformation, it adapts the R-helix structure at higher pH owing to the deprotonation of -amino groups.31-33 Similarly, shielding of cationic charge repulsion by anionic surfactant induces conformational transitions of basic peptides.34 Thus, we are interested in the effect of DNA on the secondary structure of the PLL (31) Townend, R.; Kumosinski, T. F.; Timasheff, S. N.; Fasman, G. D.; Davidson, B. Biochem. Biophys. Res. Commun. 1966, 23, 163-169. (32) Sarkar, P. K.; Doty, P. Proc. Natl. Acad. Sci. U.S.A. 1966, 55, 981-989. (33) Greenfield, N.; Fasman, G. D. Biochemistry 1969, 8, 4108-4116. (34) Ikeda, K.; Yang, J. T. Int. J. Pept. Protein Res. 1980, 16, 225-230.

Cationic Comb-Type Copolymer/DNA Interaction

Langmuir, Vol. 23, No. 1, 2007 69

Figure 7. Temperature dependence of -methylene proton resonance of the PLL backbone of PLL-g-Dex in the absence or presence of d(GGAATTCC) (N/P ) 1).

backbone of the copolymer. First, we have assessed whether the copolymer could form an R-helical structure under alkaline conditions. Whereas PLL-g-Dex alone at neutral pH exhibited CD signals consistent with the random coil conformation, that at pH 11.4 showed CD signals with strong negative bands at 207 and 222 nm characteristic of the R-helical structure. The CD spectrum at pH 11.4 of PLL-g-Dex was almost consistent with that of the PLL homopolymer (data not shown), indicating that the PLL backbone of PLL-g-Dex is capable of taking the R-helix conformation regardless of the existence of abundant graft chains. Then we assessed the influence of the ds octamers on the secondary structure of PLL-g-Dex. The ds octamers alone have weak positive signals around 210 nm. The added DNA did not cause a negative signal in the 207-222 nm range, indicating that the ds DNA did not induce an R-helix transition of the PLL backbone (Supporting Information). It is suggested that the PLL backbone kept its random conformation in the IPEC.

Conclusions Soluble IPEC formation of PLL-g-Dex and DNA allowed us to characterize the coil-helix transition of DNA in IPEC by spectrometric methods such as NMR and UV spectroscopy. The NMR chemical shifts of the nucleobase protons and their temperature dependencies implied that PLL-g-Dex did not perturb base pairs in the ds octamer. The van’t Hoff ∆H values estimated by the concentration dependency of Tm also supported the result. We have previously reported that PLL-g-Dex hardly changed the CD spectra of calf thymus and poly(dA)/poly(dT) duplex DNAs. Hence, we can conclude that the copolymer accelerates the DNA strand-exchange reaction without disordering the local structure of the initial ds DNA. As described in the previous paper,15 the strand-exchange reaction under our reaction condition required the partial melting (breathing) of the initial duplex to allow for the formation of a branched nucleation complex with the third strand. The nucleation process is considered to be the rate-determining step of the exchange reaction. Though the stabilization effect of PLL-g-Dex toward ds DNA results in reduced frequency and magnitude of the partial melting, the copolymer likely promotes the nucleation process to accelerate the exchange reaction.

The enhancement of IPEC upon the coil-helix transition of DNA was clearly observed with NMR measurements of the DNA and the copolymer. It is not surprising because ds DNA has a higher density and a larger total number of anionic charges than ss DNA and therefore has a larger extent of counterion condensation. These counterions were released upon IPEC formation with the cationic polymers, leading to more stable IPEC formation with ds DNA than with ss DNA. The IPEC formation of CCCs with DNA, however, seems to be quite sensitive to the coil-helix transition. Indeed, a very weak broadening of nucleobase proton signals by CCC was observed when non-self-complementary DNA was used. The abundant dextran grafts may sterically impede IPEC formation with ss DNA having a coiled conformation rather than ds DNA with a compact conformation. The difference in strand mobility between ss and ds DNAs might also influence complex formation. A comparative binding study with ss DNA and ds DNA or various CCCs with different grafting densities and molecular weights will be needed for a better understanding of preferential complex formation. Acknowledgment. We thank Professor M. Sekine of Tokyo Institute of Technology for valuable discussion and kind assistance with the 270 MHz NMR measurement. We also thank Fasmac Co., Ltd. for DNA synthesis and Ms. M. Saito and Dr. W. J. Kim for technical assistance. We gratefully acknowledge the Grantin-Aid for Scientific Research (no. 16200034) from the Japan Society for the Promotion of Science (JSPS), the Joint Project for Materials Chemistry, and the 21st Century COE Program, Functional Innovation of Molecular Informatics, from the Ministry of Education, Culture, Science, Sports and Technology of Japan. S.W.C. was supported by a JSPS postdoctoral fellowship. Supporting Information Available: 1H NMR spectra of the non-self-complementary ocamer in the absence or presence of PLLg-Dex, temperature dependence of dextran anomer proton resonance, and CD spectra of PLL-g-Dex/DNA mixtures. These materials are available free of charge via the Internet at http://pubs.acs.org. LA0615847