Synthesis and Physical Characterization of Bis 3′→5′ Cyclic Dinucleotides (NpNp): RNA Polymerase Inhibitors

A defined chemical synthesis of the cyclic dinucleotides, ApAp, ApUp, and UpUp has been devised, based on modern phosphotriester methods. These cyclic dinucleotides have been shown to inhibit RNA polymerase. The 1H NMR spectra of the protected dimers show a preference for the 2E form, while the spectra of the unprotected dimers show the 3E form to be favored. The circular dichroism spectra show a negative long wavelength transition; however, ApUp does not show the short wavelength maximum present in the spectra of APAP and UpUp.