Synthesis of Isoguanosine Analogues

An increasing number of isomeric (unnatural) nucleosides and nucleotides bearing an isomeric backbone, sugar or base have been characterized.1 A nucleobase isomer like isoguanine apparently makes feasible a non-standard base pair between 2`- deoxyisocytidine and 2`-deoxyisoguanosine when incorporated into oligomers. Some levels of functions by that isomeric replacement are retained and in some instances new functions are formed.2 The results reported by Switzer et al have shown that various polimerases handle this nonstandard base pair while Horn et al3 reported on the pairing in the absence of enzyme. Herein we report on a subtle change in a molecular shape by replacing N3-nitrogen with more lipophylic CH3-group and C8-H by N8-nitrogen.Though we do not prevent the Watson-Crick pairing the ring stacking might be altered. The absence of N3-nitrogen introduces an incorrectness that would disrupt the minor groove spin of hydration what means that should eliminate the presence of any ordered water molecules or metal ions at this sequence position.4 Recently,5 it has been demonstrated that in dA-dT sequences, the spine of hydration should be considered an integral part of the helix and the possible metal ions binding in the minor groove is critical for the structural integrity of duplex DNA.