Peptide Characterization and Application Protocols pp 241-267

Part of the Methods in Molecular Biology™ book series (MIMB, volume 386)

Cell-Penetrating Proline-Rich Peptidomimetics

  • Josep Farrera-Sinfreu
  • Ernest Giralt
  • Miriam Royo
  • Fernando Albericio


Cell-penetrating peptides (CPPs) offer potential as delivery agents for the cellular administration of drugs. However, the pharmacological utility of CPPs that are derived from natural amino acids is limited by their rapid metabolic degradation, low membrane permeability, and toxicity. Various peptidomimetics able to overcome these problems have been described, including peptides formed by D-amino acids and β -peptides. This chapter summarizes the synthesis of γ-proline-derived peptides and polyproline dendrimers for drug delivery applications, and includes descriptions of several modifications in the γ-peptides (mimicking the side chains of the α -amino acids) or modulating the dendrimer surface. 5(6)-Carboxyfluorescein labeling of the aforementioned peptidomimetics for use in cell translocation studies is also described. Furthermore, different protocols for the study of the drug delivery capabilities of these compounds are reviewed, including enzymatic stability studies, cellular uptake measurements by plate fluorimetry and flow cytometry, confocal laser scanning microscopy, and cytotoxicity assays.

Key Words

Cellular uptake drug delivery foldamers γ-peptides solid-phase dendrimers 


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Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  • Josep Farrera-Sinfreu
    • 1
  • Ernest Giralt
    • 2
  • Miriam Royo
    • 3
  • Fernando Albericio
    • 1
  1. 1.Barcelona Biomedical Research InstituteUniversity of BarcelonaBarcelona
  2. 2.Barcelona Biomedical Research Institute and Department of Organic ChemistryUniversity of BarcelonaBarcelona
  3. 3.Combinatorial Chemistry UnitUniversity of BarcelonaBarcelona

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