Base pairing of anhydrohexitol nucleosides with 2,6-diaminopurine, 5-methylcytosine and uracil as base moiety

Abstract

Hexitol nucleic acids (HNAs) with modified bases (5-methylcytosine, 2,6-diaminopurine or uracil) were synthesized. The introduction of the 5-methylcytosine base demonstrates that N-benzoylated 5-methylcytosylhexitol occurs as the imino tautomer. The base pairing systems (G:C(Me), U:D, T:D and U:A) obey Watson-Crick rules. Substituting hT for hU, hC(Me) for hC and hD for hA generally leads to increased duplex stability. In a single case, replacement of hC by hC(Me) did not result in duplex stabilization. This sequence-specific effect could be explained by the geometry of the model duplex used for carrying out the thermal stability study. Generally, polypurine HNA sequences give more stable duplexes with their RNA complement than polypyrimidine HNA sequences. This observation supports the hypothesis that, besides changes in stacking pattern, the difference in conformational stress between purine and pyrimidine nucleosides may contribute to duplex stability. Introduction of hC(Me) and hD in HNA sequences further increases the potential of HNA to function as a steric blocking agent.