The Library
Somatostatin subtype-2 receptor-targeted metal-based anticancer complexes
Tools
Tools
Tools
Barragán, Flavia, Carrion-Salip, Dolors, Gómez-Pinto, Irene, González-Cantó, Alejandro, Sadler, P. J., de Llorens, Rafael, Moreno, Virtudes, González, Carlos A., Massaguer, Anna and Marchán, Vicente (2012) Somatostatin subtype-2 receptor-targeted metal-based anticancer complexes. Bioconjugate Chemistry, Vol.23 (No.9). pp. 1838-1855. doi:10.1021/bc300173h ISSN 1043-1802.
|
Text
WRAP_Sadler_498_manuscript revised final form.pdf - Accepted Version Download (2389Kb) | Preview |
Official URL: http://dx.doi.org/10.1021/bc300173h
Abstract
Conjugates of a dicarba analogue of octreotide, a potent somatostatin agonist whose receptors are overexpressed on tumor cells, with [PtCl 2(dap)] (dap = 1-(carboxylic acid)-1,2-diaminoethane) (3), [(η 6-bip)Os(4-CO 2-pico)Cl] (bip = biphenyl, pico = picolinate) (4), [(η 6-p-cym)RuCl(dap)] + (p-cym = p-cymene) (5), and [(η 6-p-cym)RuCl(imidazole-CO 2H)(PPh 3)] + (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 (IC 50 = 63 ± 2 μ in MCF-7 cells and IC 50 = 26 ± 3 μ in DU-145 cells) with active participation of somatostatin receptors in cellular uptake. Similar cytotoxic activity was found in a normal cell line (IC 50 = 45 ± 2.6 μ 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. © 2012 American Chemical Society.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Subjects: | Q Science > QD Chemistry Q Science > QP Physiology |
||||
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | ||||
| Library of Congress Subject Headings (LCSH): | Somatostatin -- Receptors, Antineoplastic agents, Metal complexes -- Therapeutic use | ||||
| Journal or Publication Title: | Bioconjugate Chemistry | ||||
| Publisher: | American Chemical Society | ||||
| ISSN: | 1043-1802 | ||||
| Official Date: | September 2012 | ||||
| Dates: |
|
||||
| Volume: | Vol.23 | ||||
| Number: | No.9 | ||||
| Page Range: | pp. 1838-1855 | ||||
| DOI: | 10.1021/bc300173h | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access | ||||
| Date of first compliant deposit: | 23 December 2015 | ||||
| Date of first compliant Open Access: | 23 December 2015 | ||||
| Funder: | Spain. Ministerio de Educación y Ciencia (MEC), Catalonia (Spain), Instituto de Salud Carlos III, Universitat de Barcelona, European Research Council (ERC) | ||||
| Grant number: | CTQ2005-01834, CTQ2007-68014, CTQ2008-02064 and CTQ2010-21567 (MEC), 2009SGR208 (Catalonia), RD06/0020/0041 (ISCIII), 247450 (ERC) |
Data sourced from Thomson Reuters' Web of Knowledge
Request changes or add full text files to a record
Repository staff actions (login required)
 |
View Item |
Downloads
Downloads per month over past year
