Development of delivery carriers for plasmid DNA by conjugation of a helical template to oligoarginine

Bioorg Med Chem. 2022 Oct 15:72:116997. doi: 10.1016/j.bmc.2022.116997. Epub 2022 Sep 5.


Arginine (Arg)-rich peptides can penetrate the cell membrane and deliver nucleic acid-based therapeutics into cells. In this study, a helical template designed with a repeating sequence composed of two l-leucines (l-Leu) and a 2-aminoisobutyric acid (Aib) (l-Leu-l-Leu-Aib) was conjugated to nona-arginine on either the C- or N- terminus, designated as Block 1 and Block 2. Each terminal modification induced helical structure formation and improved the physicochemical properties of peptide/plasmid DNA (pDNA) complexes, resulting in efficient intracellular pDNA delivery. The introduction of a helical template may be effective for the endosomal escape of pDNA and pDNA release from complexes in cells. These results emphasized the potency of a helical template for the development of novel cell-penetrating peptides for pDNA delivery.

Keywords: Arginine; Cell-penetrating peptide; Gene transfer; Non-proteinogenic amino acid; Plasmid DNA delivery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arginine / chemistry
  • Cell-Penetrating Peptides* / chemistry
  • DNA / genetics
  • Leucine
  • Nucleic Acids*
  • Peptides
  • Plasmids


  • Cell-Penetrating Peptides
  • Nucleic Acids
  • Peptides
  • polyarginine
  • DNA
  • Arginine
  • Leucine