Gronewold Anja, Horn Mareike, Neundorf Ines
Department of Chemistry, Biochemistry, University of Cologne, Zuelpicher Str. 47a, 50674 Cologne, Germany.
Beilstein J Org Chem. 2018 Jun 7;14:1378-1388. doi: 10.3762/bjoc.14.116. eCollection 2018.
Within this study, we report about the design and biological characterization of novel cell-penetrating peptides (CPPs) with selective suborganelle-targeting properties. The nuclear localization sequence N50, as well as the nucleoli-targeting sequence NrTP, respectively, were fused to a shortened version of the cell-penetrating peptide sC18. We examined cellular uptake, subcellular fate and cytotoxicity of these novel peptides, N50-sC18* and NrTP-sC18*, and found that they are nontoxic up to a concentration of 50 or 100 µM depending on the cell lines used. Moreover, detailed cellular uptake studies revealed that both peptides enter cells via energy-independent uptake, although endocytotic processes cannot completely excluded. However, initial drug delivery studies demonstrated the high versatility of these new peptides as efficient transport vectors targeting specifically nuclei and nucleoli. In future, they could be further explored as parts of newly created peptide-drug conjugates.
在本研究中，我们报告了具有选择性亚细胞器靶向特性的新型细胞穿透肽（CPP）的设计和生物学特性。核定位序列N50以及核仁靶向序列NrTP分别与细胞穿透肽sC18的缩短版本融合。我们检测了这些新型肽N50-sC18和NrTP-sC18的细胞摄取、亚细胞命运和细胞毒性，发现根据所使用的细胞系，它们在浓度高达50或100μM时无毒。此外，详细的细胞摄取研究表明，尽管不能完全排除内吞过程，但这两种肽均通过能量非依赖摄取进入细胞。然而，初步的药物递送研究证明了这些新肽作为特异性靶向细胞核和核仁的高效转运载体具有高度的多功能性。未来，它们可作为新创建的肽-药物偶联物的一部分进行进一步探索。
