Probing length effects and mechanism of cell penetrating agents mounted on a polyproline helix scaffold

被引：27

作者：

Geisler, Iris ^{[1
]}

Chmielewski, Jean ^{[1
]}

机构：

[1] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 10期

关键词：

cell penetrating peptides;

D O I：

10.1016/j.bmcl.2007.02.077

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Cell penetrating peptides (CPP) displaying a type 11 polyproline helix backbone of different length and amphiphilic character were synthesized and their cellular uptake was compared. The longer CPP sequence, P14LRR, displayed a 7- to 12-fold higher uptake in MCF-7 cells as compared to its shorter counterpart, P11LRR, and a 35-fold higher uptake as compared to Tatp. These results demonstrate that an increased number of cationic and hydrophobic residues can strongly influence the extent of cellular internalization. Mechanistic investigations suggest internalization via a receptor independent endocytotic pathway with these agents. (c) 2007 Elsevier Ltd. All rights reserved.

引用

收藏

页码：2765 / 2768

页数：4

相关论文

共 46 条

[1] Tat peptide-mediated cellular delivery:: back to basics [J].

Brooks, H ;

Lebleu, B ;

Vivès, E .

ADVANCED DRUG DELIVERY REVIEWS, 2005, 57 (04) :559-577

[2]

CHRISTENSEN T, 1979, ACTA CHEM SCAND B, V33, P763, DOI 10.3891/acta.chem.scand.33b-0763

[3] Antennapedia and HIV transactivator of transcription (TAT) "protein transduction domains" promote endocytosis of high molecular weight cargo upon binding to cell surface glycosaminoglycans [J].

Console, S ;

Marty, C ;

García-Echeverría, C ;

Schwendener, R ;

Ballmer-Hofer, K .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (37) :35109-35114

[4]

DEROSSI D, 1994, J BIOL CHEM, V269, P10444

[5] Cell internalization of the third helix of the antennapedia homeodomain is receptor-independent [J].

Derossi, D ;

Calvet, S ;

Trembleau, A ;

Brunissen, A ;

Chassaing, G ;

Prochiantz, A .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (30) :18188-18193

[6] Cell-penetrating cis-γ-amino-L-proline-derived peptides [J].

Farrera-Sinfreu, J ;

Giralt, E ;

Castel, S ;

Albericio, F ;

Royo, M .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2005, 127 (26) :9459-9468

[7] Caveolae-mediated internalization of extracellular HIV-1 tat fusion proteins visualized in real time [J].

Ferrari, A ;

Pellegrini, V ;

Arcangeli, C ;

Fittipaldi, A ;

Giacca, M ;

Beltram, F .

MOLECULAR THERAPY, 2003, 8 (02) :284-294

[8] Cell penetrating agents based on a polyproline helix scaffold [J].

Fillon, YA ;

Anderson, JP ;

Chmielewski, J .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2005, 127 (33) :11798-11803

[9] Break on through to the other side - Biophysics and cell biology shed light on cell-penetrating peptides [J].

Fischer, R ;

Fotin-Mleczek, M ;

Hufnagel, H ;

Brock, R .

CHEMBIOCHEM, 2005, 6 (12) :2126-2142

[10] Decoding the entry of two novel cell-penetrating peptides in HeLa cells: Lipid raft-mediated endocytosis and endosomal escape [J].

Foerg, C ;

Ziegler, U ;

Fernandez-Carneado, J ;

Giralt, E ;

Rennert, R ;

Beck-Sickinger, AG ;

Merkle, HP .

BIOCHEMISTRY, 2005, 44 (01) :72-81

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