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

Authors: Roses, Cristina; Carbajo, Daniel; Sanclimens, Gloria; Farrera-Sinfreu, Josep; Blancafort, Adriana; Oliveras, Gloria; Cirac, Anna D.; Bardaji, Eduard; Puig, Teresa; Planas, Marta; Feliu, Lidia; Albericio, Fernando; Royo, Miriam; Tetrahedron; (2012); 10.1016/j.tet.2012.02.003

In this study, we combined a cell-penetrating γ-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 μM, 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.