Somatostatin subtype-2 receptor-targeted metal-based anticancer complexes
dc.contributor.author
dc.date.accessioned
2018-11-22T09:00:02Z
dc.date.available
2018-11-22T09:00:02Z
dc.date.issued
2012-08-08
dc.identifier.issn
1043-1802
dc.identifier.uri
dc.description.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), [(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-CO 2H)(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 μ in MCF-7 cells and IC50 = 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 (IC50 = 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
dc.format.mimetype
application/pdf
dc.language.iso
eng
dc.publisher
American Chemical Society (ACS)
dc.relation.isformatof
Versió postprint del document publicat a: https://doi.org/10.1021/bc300173h
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© Bioconjugate Chemistry, 2012, vol. 23, núm. 9, p.1838-1855
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Articles publicats (D-B)
dc.rights
Tots els drets reservats
dc.subject
dc.title
Somatostatin subtype-2 receptor-targeted metal-based anticancer complexes
dc.type
info:eu-repo/semantics/article
dc.rights.accessRights
info:eu-repo/semantics/openAccess
dc.type.version
info:eu-repo/semantics/acceptedVersion
dc.identifier.doi
dc.type.peerreviewed
peer-reviewed
dc.identifier.eissn
1520-4812