Peptide Characterization and Application Protocols

Volume 386 of the series Methods in Molecular Biology™ pp 241-267

Cell-Penetrating Proline-Rich Peptidomimetics

  • Josep Farrera-SinfreuAffiliated withBarcelona Biomedical Research Institute, University of Barcelona
  • , Ernest GiraltAffiliated withBarcelona Biomedical Research Institute and Department of Organic Chemistry, University of Barcelona
  • , Miriam RoyoAffiliated withCombinatorial Chemistry Unit, University of Barcelona
  • , Fernando AlbericioAffiliated withBarcelona Biomedical Research Institute, University of Barcelona

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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