Jump to main content
Jump to site search

Issue 17, 2016
Previous Article Next Article

Delivering aminopyridine ligands into cancer cells through conjugation to the cell-penetrating peptide BP16

Author affiliations

Abstract

Peptide conjugates incorporating the N-based ligands Me2PyTACN or (S,S′)-BPBP at the N- or the C-terminus of the cell-penetrating peptide BP16 were synthesized (PyTACN–BP16 (BP341), BP16-PyTACN (BP342), BPBP–BP16 (BP343), and BP16-BPBP (BP344)). Metal binding peptides bearing at the N-terminus the ligand, an additional Lys and a β-Ala were also prepared (PyTACN-βAK–BP16 (BP345) and BPBP-βAK–BP16 (BP346)). Moreover, taking into account the clathrin-dependent endocytic mechanism of BP16, the enzymatic cleavable tetrapeptide Gly-Phe-Leu-Gly was incorporated between the ligand and the N- or C-terminus of BP16 (BPBP-GFLG-BP16 (BP347) and BP16-GLFG-BPBP (BP348)). Analysis of the cytotoxicity of all the peptide conjugates showed that: (i) the position of the ligand influenced the IC50 values, (ii) the incorporation of the βAla-Lys dipeptide rendered non active sequences, (iii) peptide conjugates derived from the (S,S′)-BPBP ligand were more active than those bearing Me2PyTACN, and (iv) the introduction of the cleavable tetrapeptide significantly enhanced the activity of the BPBP conjugates (IC50 of 4.3 to 11.7 μM (BP347 and BP348) compared to 26.0 to >50 μM (BP343, BP344 and BP346)). The most active peptide was BPBP-GFLG-BP16 (BP347) (IC50 of 4.3 to 5.0 μM). This high activity was attributed to its high internalization in MCF-7 cells, as shown by flow cytometry, and to the subsequent release of the ligand by the intracellular cleavage of the enzyme-labile spacer, as observed in cathepsin B enzymatic assays. Therefore, these results pave the way for the design of novel peptide conjugates to be used in pro-oxidant anticancer therapies.

Graphical abstract: Delivering aminopyridine ligands into cancer cells through conjugation to the cell-penetrating peptide BP16

Back to tab navigation

Supplementary files

Publication details

The article was received on 01 Mar 2016, accepted on 01 Apr 2016 and first published on 04 Apr 2016


Article type: Paper
DOI: 10.1039/C6OB00470A
Citation: Org. Biomol. Chem., 2016,14, 4061-4070
  • Open access: Creative Commons BY-NC license
  •   Request permissions

    Delivering aminopyridine ligands into cancer cells through conjugation to the cell-penetrating peptide BP16

    M. Soler, M. González-Bártulos, E. Figueras, A. Massaguer, L. Feliu, M. Planas, X. Ribas and M. Costas, Org. Biomol. Chem., 2016, 14, 4061
    DOI: 10.1039/C6OB00470A

    This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material and it is not used for commercial purposes.

    Reproduced material should be attributed as follows:

    • For reproduction of material from NJC:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
    • For reproduction of material from PCCP:
      [Original citation] - Published by the PCCP Owner Societies.
    • For reproduction of material from PPS:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
    • For reproduction of material from all other RSC journals:
      [Original citation] - Published by The Royal Society of Chemistry.

    Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.

Search articles by author

Spotlight

Advertisements