Chemical Mutagenesis of an Emissive RNA Alphabet

An
evolved fluorescent ribonucleoside alphabet comprising isomorphic
purine (tzA, tzG) and pyrimidine (tzU, tzC) analogues, all
derived from isothiazolo­[4,3-d]­pyrimidine as a common
heterocyclic core, is described. Structural and biochemical analyses
illustrate that the nucleosides, particularly the C-nucleosidic purine analogues, are faithful isomorphic and isofunctional
surrogates of their natural counterparts and show improved features
when compared to an RNA alphabet derived from thieno­[3,4-d]-pyrimidine. The restoration of the nitrogen in a position equivalent
to the purines’ N7 leads to “isofunctional” behavior,
as illustrated by the ability of adenosine deaminase to deaminate tzA as effectively as adenosine,
the native substrate.