Development of enzyme-responsive anticancer agents and fluorescent probes targeting the biosynthesis of nucleotides

在这项研究中，我们开发了一种新的方法来合成6-磷酸肌苷的化学修饰类似物，这些类似物在核苷酸的生物合成中被观察到。为此，我们利用最近开发的一种非亲核酸性活化剂N-（氰乙基）二甲基三酸铵（CMMT），用磷酸酰胺法将羰基氧磷酸化，从而合成了磷酸基上带有不同取代基的肌苷- 6-磷酸二酯。此外，我们评估了肌苷6-磷酸二酯的稳定性，发现它们在中性水溶液中是稳定的。这些分子将有助于核苷酸生物合成的生物学和药学研究。

In this study, we developed a novel method to synthesize chemically modified analogs of inosine 6-phosphates, which are observed in the biosynthesis of nucleotides. For this purpose, we applied a non-nucleophilic acidic activator, N-(cyanomethyl)dimethylammonium triflate (CMMT), that we developed recently, to the phosphitylation of carbonyl oxygen by the phosphoramidite method, which enabled us to synthesize inosine 6-phosphate diesters bearing various substituents on the phosphate. Furthermore, we evaluated the stability of the inosine 6-phosphate diesters to find that they were stable in neutral aqueous solutions. These molecules will be useful for biological and pharmaceutical studies of the biosynthesis of nucleotides.