Cell-penetrating γ-peptide/antimicrobial undecapeptide conjugates with anticancer activity

被引：15

作者：

Roses, Cristina ^{[5
]}

Carbajo, Daniel ^{[4
]}

Sanclimens, Gloria ^{[4
]}

Farrera-Sinfreu, Josep ^{[4
]}

Blancafort, Adriana ^{[1
]}

Oliveras, Gloria ^{[1
]}

Cirac, Anna D. ^{[5
]}

Bardaji, Eduard ^{[5
]}

Puig, Teresa ^{[1
]}

Planas, Marta ^{[5
]}

Feliu, Lidia ^{[5
]}

Albericio, Fernando ^{[2
,3
]}

Royo, Miriam ^{[4
]}

机构：

[1] Univ Girona, Sch Med, Girona Biomed Res Inst IDIBGi, Girona 17071, Spain

[2] Barcelona Sci Pk, Inst Res Biomed, Barcelona 08028, Spain

[3] Univ Barcelona, Dept Organ Chem, E-08028 Barcelona, Spain

[4] Barcelona Sci Pk, Combinatorial Chem Unit, Barcelona 08028, Spain

[5] Univ Girona, LIPPSO, Dept Quim, Girona 17071, Spain

来源：

TETRAHEDRON | 2012年 / 68卷 / 23期

关键词：

gamma-Peptides; Anticancer; Antimicrobial peptides; Cell-penetrating peptides; Foldamers; HOST-DEFENSE PEPTIDES; CATIONIC ANTIMICROBIAL PEPTIDES; DE-NOVO DESIGN; BETA-PEPTIDES; FOLDAMERS; MECHANISM; DELIVERY; MOLECULES; PEPTOIDS; BIOLOGY;

D O I：

10.1016/j.tet.2012.02.003

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

In this study, we combined a cell-penetrating gamma-peptide, PEG-1, with antimicrobial undecapeptides in order to provide compounds with anticancer properties against MDA-MB-231 human breast cancer cells. We demonstrated that the conjugates were more cytotoxic than Ac-PEG-1 and the parent undecapeptides. We also evaluated the toxicity of the conjugates against non-malignant cells. The peptide conjugate with the best biological profile was BP77-PEG-1, which, at 10 mu M, showed a 71% growth inhibition in MDA-MB-231 cells and only a 17% inhibition in non-malignant cells. Therefore, this study suggests that PEG-1 mediated the undecapeptide delivery into cancer cells and that these conjugates are the proof-of-concept of this strategy to generate improved anticancer drugs based on peptides. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：4406 / 4412

页数：7

共 51 条

[1] A library of linear undecapeptides with bactericidal activity against phytopathogenic bacteria [J].

Badosa, Esther ;

Ferre, Rafael ;

Planas, Marta ;

Feliu, Lidia ;

Besalu, Emili ;

Cabrefiga, Jordi ;

Bardaji, Eduard ;

Montesinos, Emilio .

PEPTIDES, 2007, 28 (12) :2276-2285

[2] Antimicrobial Peptides - Promising Alternatives to Conventional Antibiotics [J].

Baltzer, Sylvia A. ;

Brown, Melissa H. .

JOURNAL OF MOLECULAR MICROBIOLOGY AND BIOTECHNOLOGY, 2011, 20 (04) :228-235

[3]

Brodgen N. K., 2011, INT J ANTIMICROB AG, V38, P217

[4] Peptoids that mimic the structure, function, and mechanism of helical antimicrobial peptides [J].

Chongsiriwatana, Nathaniel P. ;

Patch, James A. ;

Czyzewski, Ann M. ;

Dohm, Michelle T. ;

Ivankin, Andrey ;

Gidalevitz, David ;

Zuckermann, Ronald N. ;

Barron, Annelise E. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (08) :2794-2799

[5]

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

[6] Consequences of Isostructural Main-Chain Modifications for the Design of Antimicrobial Foldamers: Helical Mimics of Host-Defense Peptides Based on a Heterogeneous Amide/Urea Backbone [J].

Claudon, Paul ;

Violette, Aude ;

Lamour, Karen ;

Decossas, Marion ;

Fournel, Sylvie ;

Heurtault, Beatrice ;

Godet, Julien ;

Mely, Yves ;

Jamart-Gregoire, Brigitte ;

Averlant-Petit, Marie-Christine ;

Briand, Jean-Paul ;

Duportail, Guy ;

Monteil, Henri ;

Guichard, Gilles .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2010, 49 (02) :333-336

[7] 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

[8] A new class of foldamers based on cis-γ-amino-L-proline [J].

Farrera-Sinfreu, J ;

Zaccaro, L ;

Vidal, D ;

Salvatella, X ;

Giralt, E ;

Pons, M ;

Albericio, F ;

Royo, M .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2004, 126 (19) :6048-6057

[9] Inhibition of plant-pathogenic bacteria by short synthetic cecropin a-melittin hybrid peptides [J].

Ferre, Rafael ;

Badosa, Esther ;

Feliu, Lidia ;

Planas, Marta ;

Montesinos, Emili ;

Bardaji, Eduard .

APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 2006, 72 (05) :3302-3308

[10] Recent advances in the use of cell-penetrating peptides for medical and biological applications [J].

Fonseca, Sonali B. ;

Pereira, Mark P. ;

Kelley, Shana O. .

ADVANCED DRUG DELIVERY REVIEWS, 2009, 61 (11) :953-964

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