Institute for Organic Chemistry, University of Duisburg-Essen, 45117 Essen (Germany).
Angew Chem Int Ed Engl. 2015 Mar 2;54(10):2941-4. doi: 10.1002/anie.201410429. Epub 2015 Jan 22.
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.
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，它们的转染效率仍需要优化。为了实现这一目标，胍基羰基吡咯基团（专门设计的阴离子结合位点）被引入到赖氨酸的侧链中，得到了肽类似物 1。与向肽载体添加亲脂性尾巴的常见策略不同，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性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。在生理条件下平均带少于两个正电荷的 1 的转染效率甚至优于聚乙烯亚胺（PEI）。此外，1 的细胞毒性可以忽略不计，这使其成为进一步开发的有趣候选物。
