FULL PAPER A photoactivatable Pt anticancer complex conjugated to the RNA ligand guanidinoneomycin

A photoactivatable Pt 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, MS and X-ray crystallography. Photoactivation of the Ptguanidinoneomycin conjugate in the presence of 5’-GMP led to the formation of trans-[Pt(N3)(py)2(5’-GMP)] , as does the parent Pt complex. Binding of the Pt photoproduct {PtN3(py)2} + to guanine nucleobases in a short single-stranded oligonucleotide was also observed. Finally, cellular uptake studies showed that guanidinoneomycin conjugation improves the intracellular accumulation of the Pt 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.