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http://hdl.handle.net/2445/44121
Title: | Somatostatin Subtype‑2 Receptor-Targeted Metal-Based Anticancer Complexes |
Author: | Barragán, Flavia Carrión-Salip, Dolors Gómez-Pinto, Irene González-Cantó, Alejandro Sadler, Peter Llorens Duran, Rafael de Moreno Martínez, Virtudes González, Carlos Massaguer i Vall-llovera, Anna Marchán Sancho, Vicente |
Keywords: | Cèl·lules canceroses Càncer Quimioteràpia del càncer Pèptids Receptors cel·lulars Cancer cells Cancer Cancer chemotherapy Peptides Cell receptors |
Issue Date: | 2012 |
Publisher: | American Chemical Society |
Abstract: | Conjugates of a dicarba analogue of octreotide, a potent somatostatin agonist whose receptors are overexpressed on tumor cells, with [PtCl2(dap)] (dap = 1-(carboxylic acid)-1,2-diaminoethane) (3), [(η6-bip)Os(4-CO2-pico)Cl] (bip = biphenyl, pico = picolinate) (4), [(η6-p-cym)RuCl(dap)]+ (p-cym = p-cymene) (5), and [(η6-p-cym)RuCl(imidazole-CO2H)(PPh3)]+ (6), were synthesized by using a solid-phase approach. Conjugates 3-5 readily underwent hydrolysis and DNA binding, whereas conjugate 6 was inert to ligand substitution. NMR spectroscopy and molecular dynamics calculations showed that conjugate formation does not perturb the overall peptide structure. Only 6 exhibited antiproliferative activity in human tumor cells (IC50 = 63 ± 2 μM in MCF-7 cells and IC50 = 26 ± 3 μM in DU-145 cells) with active participation of somatostatin receptors in cellular uptake. Similar cytotoxic activity was found in a normal cell line (IC50 = 45 ± 2.6 μM in CHO cells), which can be attributed to a similar level of expression of somatostatin subtype-2 receptor. These studies provide new insights into the effect of receptor-binding peptide conjugation on the activity of metal-based anticancer drugs, and demonstrate the potential of such hybrid compounds to target tumor cells specifically. |
Note: | Versió postprint del document publicat a: http://dx.doi.org/10.1021/bc300173h |
It is part of: | Bioconjugate Chemistry, 2012, vol. 23, num. 9, p. 1838-1855 |
URI: | http://hdl.handle.net/2445/44121 |
Related resource: | http://dx.doi.org/10.1021/bc300173h |
ISSN: | 1043-1802 |
Appears in Collections: | Articles publicats en revistes (Química Inorgànica i Orgànica) |
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