title: Cell-penetrating proline-rich peptidomimetics.
abstract: 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 beta-peptides. This chapter summarizes the synthesis of gamma-proline-derived peptides and polyproline dendrimers for drug delivery applications, and includes descriptions of several modifications in the gamma-peptides (mimicking the side chains of the alpha-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.
authors.affiliation: Barcelona Biomedical Research Institute, University of Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Farrera-Sinfreu
authors.forename: Ernest
authors.initials: E
authors.lastname: Giralt
authors.forename: Miriam
authors.initials: M
authors.lastname: Royo
authors.forename: Fernando
authors.initials: F
authors.lastname: Albericio
mesh_terms: D000818:Animals; D032701:Biomimetics; D019556:COS Cells; D002522:Chlorocebus aethiops; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry; D016503:Drug Delivery Systems; D004355:Drug Stability; D005456:Fluorescent Dyes / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D007202:Indicators and Reagents; D018613:Microscopy, Confocal; D008967:Molecular Biology / Q000379:methods; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry*; D011392:Proline / Q000737:chemistry; D014357:Trypsin
chemical_list: D050091:Dendrimers; D004337:Drug Carriers; D005456:Fluorescent Dyes; D007202:Indicators and Reagents; D010455:Peptides; C011083:polyproline; D011392:Proline; D014357:Trypsin