Development of 2-aminoisobutyric acid (Aib)-rich cell-penetrating foldamers for efficient siRNA delivery

Chem Commun (Camb). 2019 Jul 2;55(54):7792-7795. doi: 10.1039/c9cc02203a.

Abstract

We have designed and synthesized a set of cell-penetrating foldamers (CPFs), Blocks 1-8, composed of the common amino acids Leu, Arg, and Gly, as well as the helicogenic amino acid 2-aminoisobutyric acid. The findings showed that Block 3 could deliver siRNA into cells without significant cytotoxicity. We also demonstrated that Block 3 could be applied to selectively kill the oncogene-driven cancer cells.

MeSH terms

  • Amino Acid Sequence
  • Aminoisobutyric Acids / chemistry*
  • Cell Line, Tumor
  • Cell-Penetrating Peptides / chemical synthesis
  • Cell-Penetrating Peptides / chemistry
  • Cell-Penetrating Peptides / metabolism*
  • Cell-Penetrating Peptides / toxicity
  • Drug Carriers / chemical synthesis
  • Drug Carriers / chemistry
  • Drug Carriers / metabolism*
  • Drug Carriers / toxicity
  • Gene Knockdown Techniques
  • Gene Silencing
  • Humans
  • Protein Conformation, alpha-Helical
  • Protein Engineering / methods
  • Proto-Oncogene Proteins p21(ras) / genetics
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / genetics

Substances

  • Aminoisobutyric Acids
  • Cell-Penetrating Peptides
  • Drug Carriers
  • KRAS protein, human
  • RNA, Small Interfering
  • 2-aminoisobutyric acid
  • Proto-Oncogene Proteins p21(ras)