Structural requirements for cellular uptake and antisense activity of peptide nucleic acids conjugated with various peptides.
作者： Yvonne Wolf , Stephan Pritz , Saïd Abes , Michael Bienert , Bernard Lebleu
DOI: 10.1021/BI0606896
关键词: Protein structure 、 Nucleic acid 、 Transfection 、 Biology 、 Peptide 、 Coding region 、 Linker 、 Intron 、 Biochemistry 、 Biological activity
摘要: Peptide nucleic acids (PNAs) have shown great promise as potential antisense drugs; however, poor cellular delivery limits their applications. Improved into mammalian cells and enhanced biological activity of PNAs been achieved by coupling to cell-penetrating peptides (CPPs). Structural requirements for the shuttling ability these well structural properties conjugates such linker type peptide position remained controversial, so far. In present study an 18mer PNA targeted cryptic splice site a mutated β-globin intron 2, which had inserted luciferase reporter gene coding sequence, was coupled various peptides. As lead we used α-helical amphipathic KLAL KAL KAAL KLA-NH2 [model (MAP)] varied with respect charge structure-forming properties. Furthermore, linkage localization attached (C- vs N-terminal) were modified. Positiv...
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