Helix-Stabilized Cell-Penetrating Peptides for Delivery of Antisense Morpholino Oligomers: Relationships among Helicity, Cellular Uptake, and Antisense Activity

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 t...

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Published inBioconjugate chemistry Vol. 33; no. 7; pp. 1311 - 1318
Main Authors Takada, Hiroyuki, Tsuchiya, Keisuke, Demizu, Yosuke
Format Journal Article
LanguageEnglish
Published Washington American Chemical Society 20.07.2022
Subjects
Amino acids
Cellular structure
Helicity
Membrane permeability
Oligomers
Peptides
Reagents
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Summary: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.
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ISSN:1043-1802
1520-4812
1520-4812
DOI:10.1021/acs.bioconjchem.2c00199