Alkyl chain moieties of polyamidoamine dendron-bearing lipids influence their function as a nonviral gene vector.
Alkyl chain moieties of polyamidoamine dendron-bearing lipids influence their function as a nonviral gene vector.
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DOI：
10.1021/bc060311k
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发表时间：
2007-05
影响因子：
4.7
通讯作者：
Toshinari Takahashi;C. Kojima;Atsushi Harada;K. Kono
中科院分区：
文献类型：
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作者：
Toshinari Takahashi;C. Kojima;Atsushi Harada;K. Kono
我们最近开发了一类新的阳离子脂类，它由一个聚酰胺-胺(PAMAM)树枝状分子和两个十二烷基链组成。它们的转染活性随着树枝部分的生成增加而增加[Takahashi等人。(2003)生物共轭化学。14,764-773]。本研究合成了两种不同烷基长度的PAMAM G3树枝状脂类化合物：DL-G3-2C18和DL-G3-2C12。比较了它们作为基因载体的功能。不管它们的烷基链长不同，这些树枝状脂类与质粒DNA形成的复合物具有相似的效率。然而，它们的复合体大小明显不同：DL-G3-2C18脂复合体的直径比DL-G3-2C12脂复合体的直径小得多。脂联体与肝素的相互作用表明，DL-G3-2C18脂联体比DL-G3-2C12脂联体需要更多的肝素才能使DNA从脂联体中解离。虽然在无血清条件下，DL-G3-2C12脂质体和DL-G3-2C18脂质体对CV1细胞的转染率相似，但只有后者在有血清的情况下保持了较高的转染率。这些结果表明，烷基链段的疏水相互作用对树枝状脂复合物稳定性的提高和抗血清转染性的提高起着重要的作用。
We recently developed a novel family of cationic lipids consisting of a polyamidoamine (PAMAM) dendron and two dodecyl chains. Their transfection activity increases with increasing generation of the dendron moiety [Takahashi et al. (2003) Bioconjugate Chem. 14, 764-773]. In the present study, to elucidate the effect of hydrophobic tail moieties of the dendron-bearing lipids, two kinds of PAMAM G3 dendron-bearing lipids were synthesized with different alkyl lengths, DL-G3-2C18 and DL-G3-2C12. Their functions as gene vectors were compared. Irrespective of their different alkyl chain lengths, these dendron-bearing lipids formed complexes with plasmid DNA with similar efficiency. However, their complex sizes differed markedly: DL-G3-2C18 lipoplexes exhibited much smaller diameters than DL-G3-2C12 lipoplexes. Interaction of the lipoplexes with heparin revealed that the DL-G3-2C18 lipoplexes required more heparin than DL-G3-2C12 lipoplexes to cause dissociation of plasmid DNA from the lipoplexes. Although the DL-G3-2C12 lipoplexes and DL-G3-2C18 lipoplexes transfected CV1 cells with similar efficiency in the absence of serum, only the latter retained high transfection activity in the presence of serum. These results indicate that hydrophobic interaction of alkyl chain moieties plays an important role in the increment of stability and the serum-resistant transfection activity for dendron-bearing lipid lipoplexes.