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Title: A photoactivatable PtIV anticancer complex conjugated to the RNA ligand guanidinoneomycin
Author: Shaili, Evyenia
Fernández-Giménez, Marta
Rodríguez-Astor, Savina
Gandioso, Albert
Sandín, Lluís
García-Vélez, Carlos
Massaguer i Vall-llovera, Anna
Clarkson, Guy J.
Woods, Julie A.
Sadler, Peter
Marchán Sancho, Vicente
Keywords: Medicaments antineoplàstics
Relacions estructura-activitat (Bioquímica)
Quimioteràpia del càncer
Antineoplastic agents
Structure-activity relationships (Biochemistry)
Cancer chemotherapy
Issue Date: 2-Nov-2015
Publisher: Wiley-VCH
Abstract: 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.
Note: Versió postprint del document publicat a:
It is part of: Chemistry-A European Journal, 2015, vol. 21, num. 50, p. 18474-18486
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ISSN: 0947-6539
Appears in Collections:Articles publicats en revistes (Química Inorgànica i Orgànica)

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