A photoactivatable PtIV anticancer complex conjugated to the RNA ligand guanidinoneomycin
A photoactivatable platinum(IV) complex, trans,trans,trans-[Pt(N3)2(OH)(succ)(py)2] (succ=succinylate, py=pyridine), has been conjugated to guanidinoneomycin to study the effect of this guanidinum-rich compound on the photoactivation, intracellular accumulation and phototoxicity of the pro-drug. Sur...
| Autores: | , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2015 |
| País: | España |
| Institución: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/69279 |
| Acceso en línea: | https://hdl.handle.net/2445/69279 |
| Access Level: | acceso abierto |
| Palabra clave: | Medicaments antineoplàstics ADN Fotoquímica Platí Relacions estructura-activitat (Bioquímica) Quimioteràpia del càncer Antineoplastic agents DNA Photochemistry Platinum Structure-activity relationships (Biochemistry) Cancer chemotherapy |
| Sumario: | A photoactivatable platinum(IV) complex, trans,trans,trans-[Pt(N3)2(OH)(succ)(py)2] (succ=succinylate, py=pyridine), has been conjugated to guanidinoneomycin to study the effect of this guanidinum-rich compound on the photoactivation, intracellular accumulation and phototoxicity of the pro-drug. Surprisingly, trifluoroacetic acid treatment causes the replacement of an azido ligand and the axial hydroxide ligand by trifluoroacetate, as shown by NMR spectroscopy, MS and X-ray crystallography. Photoactivation of the platinum-guanidinoneomycin conjugate in the presence of 5′-guanosine monophosphate (5′-GMP) led to the formation of trans-[Pt(N3)(py)2(5′-GMP)]+, as does the parent platinum(IV) complex. Binding of the platinum(II) photoproduct {PtN3(py)2}+ to guanine nucleobases in a short single-stranded oligonucleotide was also observed. Finally, cellular uptake studies showed that guanidinoneomycin conjugation improved the intracellular accumulation of the platinum(IV) pro-drug in two cancer cell lines, particularly in SK-MEL-28 cells. Notably, the higher phototoxicity of the conjugate in SK-MEL-28 cells than in DU-145 cells suggests a degree of selectivity towards the malignant melanoma cell line. |
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