A Tailor-Made Specific Anion-Binding Motif in the Side Chain Transforms a Tetrapeptide into an Efficient Vector for Gene Delivery
A Tailor-Made Specific Anion-Binding Motif in the Side Chain Transforms a Tetrapeptide into an Efficient Vector for Gene Delivery
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DOI：
10.1002/anie.201410429
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发表时间：
2015-03-02
影响因子：
16.6
通讯作者：
Schmuck, Carsten
中科院分区：
文献类型：
--
作者：
Li, Mao;Schlesiger, Stefanie;Schmuck, Carsten
富含精氨酸的细胞穿透肽被广泛用作基因传递的载体。然而，它们的转染功效仍需要优化。为了实现这一目标，将定制的阴离子结合位点胍基羰基吡咯基团引入四赖氨酸的侧链以获得肽类似物1。与向肽载体添加亲脂性尾部的常见策略相反，这种新方法很可能通过结合基序与DNA或细胞膜之间更特异的相互作用来增强转染效率。因此，四肽类似物1是迄今为止报道的最小的肽转染载体。 1在生理条件下平均带有少于两个正电荷，其转染效果甚至优于聚乙烯亚胺（PEI）。此外，1 仅表现出可忽略不计的细胞毒性，这使其成为进一步开发的有趣候选者。
Arginine-rich cell-penetrating peptides are widely utilized as vectors for gene delivery. However, their transfection efficacy still needs to be optimized. To accomplish this, guanidinocarbonylpyrrole groups, which are tailor-made anion binding sites, were introduced into the side chains of tetralysine to obtain the peptide analogue 1. In contrast to the common strategy of adding a lipophilic tail to peptide vectors, this novel method most likely enhances transfection efficacy through more specific interactions between the binding motifs and DNA or the cell membrane. Tetrapeptide analogue 1 is thus the smallest peptidic transfection vector that has been reported to date. The transfection efficacy of 1, which on average has less than two positive charges under physiological conditions, is even better than that of polyethylenimine (PEI). Furthermore, 1 exhibits only negligible cytotoxicity, which makes it an interesting candidate for further development.