Small-molecule mimics of an alpha-helix for efficient transport of proteins into cells

Nat Methods. 2007 Feb;4(2):153-9. doi: 10.1038/nmeth997. Epub 2007 Jan 14.


We designed and synthesized small-molecule mimics of an alpha-helical peptide protein transduction domain (PTD). These small-molecule carriers, which we termed SMoCs, are easily coupled to biomolecules, and efficiently deliver dye molecules and recombinant proteins into a variety of cell types. We designed the SMoCs using molecular modeling techniques. As an example of a protein cargo, we applied this new technology to the internalization of the DNA replication licensing repressor geminin, in vitro, providing evidence that extracellularly delivered SMoC-geminin can have an antiproliferative effect on human cancer cells. Uptake of SMoC-geminin was inhibited at 4 degrees C and by chlorpromazine, a compound that induces misassembly of clathrin-coated pits at the cell surface. Thus the mechanism of uptake is likely to be clathrin-mediated endocytosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antennapedia Homeodomain Protein / chemistry
  • Biphenyl Compounds
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • Cells, Cultured
  • Clathrin / metabolism
  • Coated Pits, Cell-Membrane / chemistry
  • Coloring Agents / chemistry
  • Coloring Agents / metabolism
  • Endocytosis
  • Geminin
  • HeLa Cells
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Mice
  • Molecular Mimicry*
  • NIH 3T3 Cells
  • Peptides / chemistry
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Protein Transport*


  • Antennapedia Homeodomain Protein
  • Biphenyl Compounds
  • Cell Cycle Proteins
  • Clathrin
  • Coloring Agents
  • GMNN protein, human
  • Geminin
  • Peptides
  • diphenyl