Synthesis and Enzymatic Digestion of an RNA Nonamer in Both Enantiomeric Forms

The d- and l-RNA nonamers of the sequence r(GCUUCGGC)T have been synthesised for X-ray crystallographic purposes. In vitro digestion of the unnatural optical antipode by snake venom phosphodiesterase I takes place at an approximately 1800-fold slower rate than that of the natural d-nonamer. The digestion experiments showed—to our knowledge for the first time—that l-RNA can indeed be cleaved enzymatically when phosphodiesterase I from snake venom is used—as opposed to a number of cellular ribonucleases—which sheds an interesting light on the evolution and possibly structure/function relationship of venom versus cellular degradation enzymes. The broad substrate specificity of this enzyme could be taken advantage of to study and further optimise the resistance towards biodegradation of therapeutic l-RNA aptamers.