Replacement of a proline with silaproline causes a 20-fold increase in the cellular uptake of a Pro-rich peptide

J Am Chem Soc. 2006 Jul 5;128(26):8479-83. doi: 10.1021/ja060036c.

Abstract

The results presented here show that elementary design enhancements have led to a 20-fold increase in the cellular uptake properties of a Pro-rich cell-penetrating peptide. These results are relevant not only due to the increasing interest in using CPPs as molecular shuttles for intracellular drug delivery but also because they illustrate the power of combining conformational analysis with rational design to modulate the behavior of biologically active compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Survival / drug effects
  • Circular Dichroism / methods
  • Drug Carriers / chemical synthesis
  • Drug Carriers / chemistry
  • Drug Carriers / pharmacokinetics*
  • HeLa Cells
  • Humans
  • Microscopy, Electron, Transmission / methods
  • Molecular Conformation
  • Organosilicon Compounds / chemistry
  • Organosilicon Compounds / metabolism*
  • Peptides / chemical synthesis
  • Peptides / chemistry
  • Peptides / pharmacokinetics*
  • Proline / analogs & derivatives*
  • Proline / chemistry
  • Proline / metabolism*
  • Proline-Rich Protein Domains
  • Protein Transport / drug effects
  • Sensitivity and Specificity
  • Structure-Activity Relationship

Substances

  • Drug Carriers
  • Organosilicon Compounds
  • Peptides
  • silaproline
  • Proline