Helix-Stabilized Cell-Penetrating Peptides for Delivery of Antisense Morpholino Oligomers: Relationships among Helicity, Cellular Uptake, and Antisense Activity.
Hiroyuki TakadaKeisuke TsuchiyaYosuke DemizuPublished in: Bioconjugate chemistry (2022)
The secondary structures of cell-penetrating peptides (CPPs) influence their properties including their cell-membrane permeability, tolerability to proteases, and intracellular distribution. Herein, we developed helix-stabilized arginine-rich peptides containing α,α-disubstituted α-amino acids and their conjugates with antisense phosphorodiamidate morpholino oligomers (PMOs), to investigate the relationships among the helicity of the peptides, cellular uptake, and antisense activity of the peptide-conjugated PMOs. We demonstrated that helical CPPs can efficiently deliver the conjugated PMO into cells compared with nonhelical CPPs and that their antisense activities are synergistically enhanced in the presence of an endosomolytic reagent or an endosomal escape domain peptide.
Keyphrases
- amino acid
- nucleic acid
- single cell
- induced apoptosis
- cell therapy
- photodynamic therapy
- nitric oxide
- dna binding
- endothelial cells
- clinical trial
- randomized controlled trial
- endoplasmic reticulum stress
- oxidative stress
- drug delivery
- mesenchymal stem cells
- cell death
- reactive oxygen species
- bone marrow
- mass spectrometry
- placebo controlled