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

被引：14

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

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