Key Laboratory of Hubei Province for Coal Conversion and New Carbon Materials; School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan 430081, P. R. China.
Beijing National Laboratory for Molecular Sciences; National Centre for Mass Spectrometry in Beijing; CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China.
Dalton Trans. 2022 Aug 9;51(31):11834-11839. doi: 10.1039/d2dt01719a.
Photoactivatable Pt(IV) anticancer prodrug ,,-[Pt(N)(OH)(pyridine)] (1) has been shown to bind to and induce oxidation of all four DNA nucleobases. Herein, to further render the binding spectrum of complex 1 to nucleic acids, the interaction between complex 1 and uridine, an exclusive RNA component, was investigated by electrospray ionization mass spectrometry (ESI-MS) and NMR spectroscopy. The results showed that complex 1 can bind to uridine through the N3 (major) and O4 (minor) sites upon light irradiation to form the major mono-platinated uridine adduct and the minor di-platinated uridine adduct. Moreover, mono-platinated uridine associated with the oxidation of uridine to 5-hydroxyuridine and 6-hydroxyuridine was also observed. This is the first report that the photoactivatable Pt(IV) prodrug binds to and induces the oxidation of uridine, and also the last piece of the puzzle for the interactions of complex 1 with nucleobases. Combined with our previous results about the interactions between complex 1 and DNA bases, these data showed a wide interaction spectrum of this kind of photoactivatable diazido Pt(IV) prodrugs with nucleobases through such dual-action modes, strongly suggesting that RNA may be a potential target of Pt(IV) prodrugs.
光激活型顺铂（IV）抗癌前药， - [Pt（N）（OH）（吡啶）]（1）已被证明能与所有四个 DNA 碱基结合并诱导其氧化。在此，为了进一步扩展配合物 1 与核酸的结合谱，通过电喷雾电离质谱（ESI-MS）和 NMR 光谱研究了配合物 1 与尿嘧啶（一种独特的 RNA 成分）之间的相互作用。结果表明，配合物 1 可在光照下通过 N3（主要）和 O4（次要）位点与尿嘧啶结合，形成主要的单铂化尿嘧啶加合物和次要的二铂化尿嘧啶加合物。此外，还观察到与尿嘧啶氧化为 5-羟基尿嘧啶和 6-羟基尿嘧啶相关的单铂化尿嘧啶。这是首例报道光激活型顺铂（IV）前药与尿嘧啶结合并诱导其氧化的报道，也是配合物 1 与碱基相互作用的最后一块拼图。结合我们之前关于配合物 1 与 DNA 碱基相互作用的结果，这些数据表明，通过这种双重作用模式，这种光激活型叠氮顺铂（IV）前药与碱基具有广泛的相互作用谱，强烈提示 RNA 可能是顺铂（IV）前药的潜在靶标。
