Synthesis of Novel Polyampholyte Comb-Type Copolymers Consisting of a Poly(L-lysine) Backbone and Hyaluronic Acid Side Chains for a DNA Carrier
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- 作者：Shoichiro Asayama ; Masayuki Nogawa ; Yoshiyuki Takei ; Toshihiro Akaike ; and Atsushi Maruyama
- 刊名：Bioconjugate Chemistry
- 出版年：1998
- 出版时间：July 1998
- 年：1998
- 卷：9
- 期：4
- 页码：476 - 481
- 全文大小：178K
- 年卷期：v.9,no.4(July 1998)
- ISSN：1520-4812
文摘
The polyampholyte comb-type copolymers consisting of a poly(L-lysine) (PLL) main chain, a DNAbinding site, and hyaluronic acid (HA) side chains, cell-specific ligands, have been prepared as theDNA carrier targeting sinusoidal endothelial cells of liver. The reducing end of HA and 
-amino groupsof 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-molecularweight HA. Since HA formed polyion complexes with PLL, the coupling reaction was carried outwith high-ionic strength media to suppress polyion complex formation. The reaction proceeded in ahomogeneous 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 PLLwith high-ionic strength media, it is possible to prepare the various comb-type copolymers with adefined density and a defined length of HA side chains. Furthermore, we also find that thesepolyampholyte comb-type copolymers vary their assembling structure in water in response to twokinds of environmental factors, i.e., ionic strength and pH. Finally, a 1H NMR study reveals that thePLL backbone efficiently interacts with DNA molecules despite the presence of HA side chains havingnegative charges.
-amino groupsof 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-molecularweight HA. Since HA formed polyion complexes with PLL, the coupling reaction was carried outwith high-ionic strength media to suppress polyion complex formation. The reaction proceeded in ahomogeneous 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 PLLwith high-ionic strength media, it is possible to prepare the various comb-type copolymers with adefined density and a defined length of HA side chains. Furthermore, we also find that thesepolyampholyte comb-type copolymers vary their assembling structure in water in response to twokinds of environmental factors, i.e., ionic strength and pH. Finally, a 1H NMR study reveals that thePLL backbone efficiently interacts with DNA molecules despite the presence of HA side chains havingnegative charges.