Synthesis of novel polyampholyte comb-type copolymers consisting of a poly(L-lysine) backbone and hyaluronic acid side chains for a DNA carrier
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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DOI：
10.1021/bc970213m
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发表时间：
1998-07-01
影响因子：
4.7
通讯作者：
Maruyama, A
中科院分区：
文献类型：
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作者：
Asayama, S;Nogawa, M;Maruyama, A
以聚L-赖氨酸（PLL）主链为DNA结合位点，透明质酸（HA）侧链为细胞特异性配体，制备了梳型两性聚电解质共聚物作为肝窦内皮细胞靶向DNA载体。HA的还原端与PLL的E-氨基通过还原胺化共价偶联，得到所得梳型共聚物（PLL-graft-HA）。HA的链长由高分子量HA的酶解控制。由于HA与PLL形成聚离子复合物，因此用高离子强度介质进行偶联反应以抑制聚离子复合物的形成。反应在均相体系中进行，导致HA偶联到PLL主链上的高效率（>70%）。通过使用HA的酶促水解和HA与PLL之间用高离子强度介质的还原胺化反应，可以制备具有限定密度和限定长度的HA侧链的各种梳型共聚物。此外，我们还发现，这些聚两性电解质梳型共聚物在水中响应于两种环境因素而改变其组装结构，即，最后，1H-1 NMR研究揭示，尽管存在具有负电荷的HA侧链，PLL主链仍有效地与DNA分子相互作用。
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 E-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 H-1 NMR study reveals that the PLL backbone efficiently interacts with DNA molecules despite the presence of HA side chains having negative charges.