We discovered a new class of artificial peptidic transfection vectors based on an artificial anion binding motif, the guanidiniocarbonylpyrrole cation (abbreviated as GCP). This new type of vector is surprisingly small compared to traditional systems and our previous work suggested that the GCP group is important for promoting the critical endosomal escape. We now present here a systematic comparison of similar DNA-ligands featuring our GCP oxo-anion binding motif with DNA-ligands only consisting of natural occurring amino acids. Structure-activity studies showed that the artificial binding motif clearly outperforms natural amino acids such as histidine, lysine and arginine. It improved the ability to shuttle foreign genetic material into cells, yet successfully mediated endosomal escape. Also plasmids that are complexed by our artificial ligands are stabilized against cytosolic degradation to some extent. This resulted in the successful expression of plasmid information (comparable to gold standards like PEI). Hence, our study clearly demonstrates the importance of the tailor-made GCP anion binding site for efficient gene transfection.

中文翻译：

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新型小肽转染载体的系统结构活性研究揭示了特殊的氧阴离子结合基序对于基因传递的重要性。

我们发现了基于人工阴离子结合基序的新一类人工肽转染载体，胍基羰基吡咯阳离子（缩写为GCP）。与传统系统相比，这种新型载体体积小得令人惊讶，我们的先前工作表明，GCP组对于促进关键的内体逃逸至关重要。现在，我们在这里对具有我们的GCP氧阴离子结合基序的类似DNA配体与仅由天然氨基酸组成的DNA配体进行系统比较。结构活性研究表明，人工结合基序明显优于天然氨基酸，例如组氨酸，赖氨酸和精氨酸。它提高了将外来遗传物质穿梭到细胞中的能力，但却成功地介导了内体逃逸。而且，由我们的人工配体复合的质粒在一定程度上可以稳定地抵抗细胞质降解。这导致质粒信息的成功表达（相当于金标准，如PEI）。因此，我们的研究清楚地证明了量身定制的GCP阴离子结合位点对于有效基因转染的重要性。