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  • Title: Reactions of a photoactivatable diazido Pt(iv) anticancer complex with a single-stranded oligodeoxynucleotide.
    Author: Liang Z, Lin J, Gong X, Cheng Y, Huang C, Zhang J, Wu X, Wang F, Zhao Y, Wu K.
    Journal: Dalton Trans; 2020 Aug 18; 49(32):11249-11259. PubMed ID: 32756682.
    Abstract:
    Platinum based anticancer agents are widely applied in clinic and their major target is believed to be DNA. Herein, the interaction of a photoactivatable diazido Pt(iv) anticancer prodrug trans,trans,trans-[Pt(N3)2(OH)2(py)2] (py = pyridine; 1) with a 15-mer single-G-containing oligodeoxynucleotide (ODN I: 5'-CT2CTCTTG8T9CT11TCTC-3') was investigated by mass spectrometric methods. Up to penta-platinated ODN I adducts were identified from primary mass spectra while the mono- and di-platinated adducts had the highest intensity. Fragmentation of mono-, di- and tri-platinated I adducts in tandem MS revealed that T2, G8, T11 and T9 are binding sites. No cytosine sites were identified which may be due to the facile loss of Pt adducts from cytosine during CID. The intensity of {Pt(py)2}-bound adducts was comparable to that of {Pt(N3)(py)2}-bound adducts, indicating that the photo-reduction pathway of complex 1 from Pt(iv) to Pt(ii) through two one-electron donations from two azides was substantial. Moreover, no transformation of N3 to NH3 on the {Pt(N3)(py)2}-bound adducts was observed, whereas it is very popular during the reactions of complexes with short ODNs or mono-nucleotides. The oxidation on I induced by the reactive oxygen species (ROS) formed by the photodecomposition of complex 1 was significant, and the oxidation of G8 to 8-hydroxyguanine (8-OH-G), spiroiminodihydantoin (Sp) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG) was discovered. These results unambiguously revealed a sequence-length-dependent photochemical reactivity of complex 1 when it interacted with different ODNs, providing deeper understanding in the reactivity of photoactivatable diazido anticancer Pt(iv) prodrugs to DNA.
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