Development of cationic oligodiaminogalactoses specifically binding to duplex RNA, but not to duplex DNA

Duplex RNA stabilization is important for the application in the artificial silencing of gene expression. Excess usage of cationic molecules with low binding affinity to duplex RNA may cause cytotoxicity due to nonspecific binding. Cationic molecules specifically binding to duplex RNA with high binding affinity are necessary for duplex RNA stabilization. Here, UV melting and isothermal titration calorimetric analyses revealed that our previously designed cationic oligodiaminogalactose 4 mer (ODAGal4) specifically stabilized duplex RNA by binding to it with approximately 10⁵ M⁻¹ binding constant, without binding to duplex DNA. Temperature dependence of thermodynamic parameters, including negative enthalpy and entropy changes, revealed that the magnitude of negative heat capacity change was quite large for small molecules binding to duplex RNA, suggesting the influence of the hydrophobic effect on the binding process. Our results suggest the therapeutic application of ODAGal4 as a key molecule for duplex RNA-binding specificity to prevent any nonspecific binding.