Synthesis of novel polyampholyte comb-type copolymers consisting of a poly(L-lysine) backbone and hyaluronic acid side chains for a DNA carrier.
The polyampholyte comb-type copolymers consisting of a poly(L-lysine) (PLL) main chain, a DNA binding site, and hyaluronic acid (HA) side chains, cell-specific ligands, have been prepared as the DNA carrier targeting sinusoidal endothelial cells of liver. The reducing end of HA and epsilon-amino groups of PLL were covalently coupled by reductive amination to obtain the resulting comb-type copolymers (PLL-graft-HA). The chain length of HA was controlled by the enzymatic hydrolysis of high-molecular weight HA. Since HA formed polyion complexes with PLL, the coupling reaction was carried out with high-ionic strength media to suppress polyion complex formation. The reaction proceeded in a homogeneous system, leading to a high efficiency of coupling (>70%) of HA onto the PLL backbone. By using the enzymatic hydrolysis of HA and the reductive amination reaction between HA and PLL with high-ionic strength media, it is possible to prepare the various comb-type copolymers with a defined density and a defined length of HA side chains. Furthermore, we also find that these polyampholyte comb-type copolymers vary their assembling structure in water in response to two kinds of environmental factors, i.e., ionic strength and pH. Finally, a 1H NMR study reveals that the PLL backbone efficiently interacts with DNA molecules despite the presence of HA side chains having negative charges.
Department of Biomolecular Engineering, Tokyo Institute of Technology, 4259 Nagatsuta, Midori, Yokohama 226-8501, Japan.
S
S
Asayama
M
M
Nogawa
Y
Y
Takei
T
T
Akaike
A
A
Maruyama
D002240:Carbohydrate Sequence; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004247:DNA / Q000737:chemistry; D006820:Hyaluronic Acid / Q000138:chemical synthesis* / Q000737:chemistry; D008969:Molecular Sequence Data; D011107:Polylysine / Q000138:chemical synthesis*; D011108:Polymers / Q000138:chemical synthesis*
D011108:Polymers; D011107:Polylysine; D006820:Hyaluronic Acid; D004247:DNA