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Title: Somatostatin Subtype‑2 Receptor-Targeted Metal-Based Anticancer Complexes
Author: Barragán, Flavia
Carrión-Salip, Dolors
Gómez-Pinto, Irene
González-Canto, Alejandro
Sadler, Peter
Llorens, Rafael de
Moreno Martínez, Virtudes
González, Carlos
Massaguer i Vall-llovera, Anna
Marchán Sancho, Vicente
Keywords: Cèl·lules canceroses
Quimioteràpia del càncer
Receptors cel·lulars
Cancer cells
Cancer chemotherapy
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:
It is part of: Bioconjugate Chemistry, 2012, vol. 23, num. 9, p. 1838-1855
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ISSN: 1043-1802
Appears in Collections:Articles publicats en revistes (Química Inorgànica i Orgànica)

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