De Novo Design of Cell-Penetrating Foldamers

Chem Rec. 2020 Sep;20(9):912-921. doi: 10.1002/tcr.202000047. Epub 2020 May 28.


Cell-penetrating peptides (CPPs) have gained much attention as carriers of hydrophilic molecules, such as drugs, peptides, and nucleic acids, into cells. CPPs are mainly composed of cationic amino acid residues, which play an important role in their intracellular uptake via interactions with acidic groups on cell surfaces. In addition, the secondary structures of CPPs also affect their cell-membrane permeability. Based on this knowledge, a variety of cell-penetrating foldamers (oligomers that form organized secondary structures) have been developed to date. In this account, we describe recent attempts to develop cell-penetrating foldamers containing various building blocks, and their application as DDS carriers.

Keywords: DDS carrier; cell-penetrating peptide; foldamer; non-proteinogenic amino acid; secondary structure.

Publication types

  • Review

MeSH terms

  • Amino Acids / chemistry
  • Cell-Penetrating Peptides / chemistry*
  • Cell-Penetrating Peptides / metabolism
  • Drug Carriers / chemistry
  • Humans
  • Peptides, Cyclic / chemistry
  • Peptoids / chemistry
  • Proline / chemistry
  • Urea / chemistry


  • Amino Acids
  • Cell-Penetrating Peptides
  • Drug Carriers
  • Peptides, Cyclic
  • Peptoids
  • Urea
  • Proline