Junghänel Sandra, Karczewski Sarah, Bäcker Sandra, Knauer Shirley K, Schmuck Carsten
Institute of Organic Chemistry, University of Duisburg-Essen, Universitätsstrasse 7, 45117, Essen, Germany.
Institute of Molecular Biology, University of Duisburg-Essen, Universitätsstrasse 7, 45117, Essen, Germany.
Chembiochem. 2017 Nov 16;18(22):2268-2279. doi: 10.1002/cbic.201700433. Epub 2017 Oct 25.
We discovered a new class of artificial peptidic transfection vectors based on an artificial anion-binding motif, the guanidiniocarbonylpyrrole (GCP) cation. This new type of vector is surprisingly smaller than traditional systems, and our previous work suggested that the GCP group was important for promoting 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 naturally occurring amino acids. Structure-activity studies showed that the artificial binding motif clearly outperformed 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 were complexed by our artificial ligands were stabilized against cytosolic degradation to some extent. This resulted in the successful expression of plasmid information (comparable to gold standards such as polyethyleneimine). Hence, our study clearly demonstrates the importance of the tailor-made GCP anion-binding site for efficient gene transfection.
我们基于一种人工阴离子结合基序——胍基羰基吡咯（GCP）阳离子，发现了一类新型的人工肽类转染载体。这种新型载体令人惊讶地比传统系统更小，并且我们之前的研究表明GCP基团对于促进关键的内体逃逸很重要。我们现在在此展示了对具有我们的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配体的系统比较。构效关系研究表明，人工结合基序明显优于组氨酸、赖氨酸和精氨酸等天然氨基酸。它提高了将外源遗传物质转运到细胞中的能力，并且成功介导了内体逃逸。此外，与我们的人工配体复合的质粒在一定程度上对胞质降解具有稳定性。这导致了质粒信息的成功表达（与聚乙烯亚胺等金标准相当）。因此，我们的研究清楚地证明了定制的GCP阴离子结合位点对于高效基因转染的重要性。
