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Current Pharmaceutical Design
ISSN (Print): 1381-6128
ISSN (Online): 1873-4286
VOLUME: 11
ISSUE: 28
DOI: 10.2174/138161205774580796      Price:  $58









Cell-Penetrating Peptides: Mechanisms and Applications

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Author(s): S. El-Andaloussi, T. Holm and U. Langel
Pages 3597-3611 (15)
Abstract:
A major obstacle in the development of new therapeutic agents is the low bioavailability of hydrophilic substances. Drugs that bind to intracellular targets must penetrate the lipid bilayer surrounding the cell in order to exert their effect. A relatively new research area that addresses this problem by introducing novel transport peptides that facilitate the cellular penetration of potential drugs has emerged. These peptides predominantly have a positive net charge and/or an amphipathic nature, but can otherwise have very different characteristics. This group of peptides, although sometimes called protein transduction domains (PTDs), is here referred to as cell-penetrating peptides (CPPs). For many years it was believed that these peptides were internalized into cells via a non-endocytotic, receptorindependent pathway. However, recent publications have suggested that an endocytotic pathway cannot be ruled out, and that earlier results might be based on artifacts associated with fixation of cells and membrane association of peptides. Although the mechanism of cellular uptake remains unclear, there is an increasing amount of reports on biological effects of CPPs and their cargos. Thus, CPPs are an attractive pharmaceutical and biochemical tool that needs more attention. This review will discuss some recent results in this research field with focus on the cell-penetrating peptide transportan.
Keywords:
cell-penetrating peptides, transportan, cargo delivery, protein transduction, endocytosis
Affiliation:
Department of Neurochemistry and Neurotoxicology, Stockholm University, S. Arrheniusv 21A,SE-10691 Stockholm Sweden.