Use of pKa differences to enhance the formation of base triplets involving C-G and G-C base pairs

Two C-nucleosides are employed for the recognition of dC-dG base pairs. Both derivatives are related to dC but lack, the Oa-carbonyl. The absence of the carbonyl should eliminate any unfavorable steric interactions at this site. One of the derivatives contains a a-aminopyridine heterocycle (d2APy) while the second contains a 2-aminopyrimidine heterocycle (d2APm). The former with a pK(a) of 6.8 functions better for the recognition of dG-dC base pairs than it does in the binding to dC-dG lease pairs. The d2APm derivative with a pK(a) of 3.3 functions better to form base triplets with dC-dG base pairs than with dG-dC targets. Tripler T-m's in both cases are compared with the sequence containing the native dC residue. The dC analogues appear to make two hydrogen bonds to a target dG base residue, one of which requires protonation of the ring nitrogen. Recognition of a target dC residue appears to require the formation of a single hydrogen bond to the C-nucleoside and having that nitrogen largely in the unprotonated state facilitates its formation.