Cell-penetrating peptides:: Mechanisms and applications

被引:191
作者
El-Andaloussi, S [1 ]
Holm, T [1 ]
Langel, Ü [1 ]
机构
[1] Stockholm Univ, Dept Neurochem & Neutotoxicol, SE-10691 Stockholm, Sweden
关键词
cell-penetrating peptides; transportan; cargo delivery; protein transduction; endocytosis;
D O I
10.2174/138161205774580796
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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, receptor-independent 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.
引用
收藏
页码:3597 / 3611
页数:15
相关论文
共 135 条
[41]  
GOTTSCHALK S, 1996, GENE THER, V3, P48
[42]   AUTONOMOUS FUNCTIONAL DOMAINS OF CHEMICALLY SYNTHESIZED HUMAN IMMUNODEFICIENCY VIRUS TAT TRANS-ACTIVATOR PROTEIN [J].
GREEN, M ;
LOEWENSTEIN, PM .
CELL, 1988, 55 (06) :1179-1188
[43]   Cargo delivery kinetics of cell-penetrating peptides [J].
Hällbrink, M ;
Florén, A ;
Elmquist, A ;
Pooga, M ;
Bartfai, T ;
Langel, Ü .
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 2001, 1515 (02) :101-109
[44]   Direct translocation of histone molecules across cell membranes [J].
Hariton-Gazal, E ;
Rosenbluh, J ;
Graessmann, A ;
Gilon, C ;
Loyter, A .
JOURNAL OF CELL SCIENCE, 2003, 116 (22) :4577-4586
[45]   Consequences of nonlytic membrane perturbation to the translocation of the cell penetrating peptide pep-1 in lipidic vesicles [J].
Henriques, ST ;
Castanho, MARB .
BIOCHEMISTRY, 2004, 43 (30) :9716-9724
[46]   Rapid induction of apoptosis mediated by peptides that bind initiation factor eIF4E [J].
Herbert, TP ;
Fåhraeus, R ;
Prescott, A ;
Lane, DP ;
Proud, CG .
CURRENT BIOLOGY, 2000, 10 (13) :793-796
[47]  
Hong FD, 2000, CANCER RES, V60, P6551
[48]   Intracellular delivery of bioactive peptides to RBL-2H3 cells induces β-hexosaminidase secretion and phospholipase D activation [J].
Howl, J ;
Jones, S ;
Farquhar, M .
CHEMBIOCHEM, 2003, 4 (12) :1312-1316
[49]   Complexes of plasmid DNA with basic domain 47-57 of the HIV-1 Tat protein are transferred to mammalian cells by endocytosis-mediated pathways [J].
Ignatovich, IA ;
Dizhe, EB ;
Pavlotskaya, AV ;
Akifiev, BN ;
Burov, SV ;
Orlov, SV ;
Perevozchikov, AP .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (43) :42625-42636
[50]   The use of cell-penetrating peptides as a tool for gene regulation [J].
Järver, P ;
Langel, Ü .
DRUG DISCOVERY TODAY, 2004, 9 (09) :395-402