A Helix-Stabilized Cell-Penetrating Peptide as an Intracellular Delivery Tool

Chembiochem. 2016 Jan;17(2):137-40. doi: 10.1002/cbic.201500468. Epub 2015 Dec 3.

Abstract

Two types of cationic cyclic α,α-disubstituted α-amino acids: ApiC2NH2 (which possesses a lysine mimic side chain) and Api(C2Gu) (which possesses an arginine mimic side chain), were developed. These amino acids were incorporated into an arginine-based peptide sequence [(L-Arg-L-Arg-dAA)3: dAA=ApiC2NH2 or Api(C2Gu)], and the relationship between the secondary structures of the resulting peptides and their ability to pass through cell membranes was investigated. The peptide containing Api(C2Gu) formed a stable α-helical structure and was more effective at penetrating cells than the nonhelical Arg nonapeptide (R9). Furthermore, the peptide was able to deliver plasmid DNA into various types of cells in a highly efficient manner.

Keywords: cell-penetrating peptides; helical structure; non-proteinogenic amino acids; plasmid DNA delivery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell-Penetrating Peptides / chemistry*
  • Circular Dichroism
  • HeLa Cells
  • Humans
  • Models, Biological
  • Molecular Structure
  • Plasmids / chemistry*

Substances

  • Cell-Penetrating Peptides