Intrinsically cell-permeable miniature proteins based on a minimal cationic PPII motif

J Am Chem Soc. 2007 Nov 28;129(47):14578-9. doi: 10.1021/ja0772445. Epub 2007 Nov 6.

Abstract

Cell-penetrating peptides (CPPs) provide promising tools for the cellular delivery of molecular cargos ranging in size from small molecules and peptides to proteins and quantum dots. CPPs are typically cationic and/or amphipathic sequences that are unstructured or alpha-helical. We expand the repertoire of cell-penetrating motifs by designing encodable CPPs possessing type-II polyproline (PPII) helical structure. These motifs surpass the uptake efficiency of existing CPPs and are not cytotoxic at concentrations 100 times greater than that necessary for delivery. By replacing the PPII helix of a miniature protein, the motif can endow intrinsic cell permeability without increasing molecular size.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Cations
  • Cell Membrane Permeability
  • Circular Dichroism
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Peptides / chemistry*
  • Proteins / chemistry*
  • Proteins / metabolism*

Substances

  • Cations
  • Peptides
  • Proteins
  • polyproline