Mismatch Discrimination of Base-Modified Nucleic Acids and their Constituents: Non-Watson-Crick Base Pairing Induced by Tautomerization

Abstract

The effect of tautomerism on the mismatch discrimination was studied on 7-deazapurine and 8-aza-7-deazapurine analogues of isoguanosine. 7-Halogenated 7-deaza-2′-deoxyisoguanosines show better base pair discrimination than 2′-deoxyisoguanosine due to the more favored keto tautomer formation. 8-Aza-7-deazaisoguanosine and its 7-halogeno derivatives also show higher keto tautomer population than that of isoguanosine, but the 7-halogens do not bias the tautomeric equilibrium significantly as it is observed for the 7-deaza-2′-deoxyisoguanosine derivatives.

Keywords:

• Nucleosides
• oligonucleotides
• 7-deazapurines
• 8-aza-7-deazapurines
• base pair discrimination
• tautomers

Financial support by the Bundesministerium für Forschung and Technologie (ChemBiotech, Germany), Idenix Pharmaceuticals (USA), and the Roche Diagnostics GmbH (Germany) is gratefully acknowledged.

Notes

^a Measured in 1.0 M NaCl, 0.1 M MgCl₂, and 60 mM Na-cacodylate buffer, pH 7.0, with 5 μM + 5 μ M single-strand concentration.

^b The data in parentheses are Δ T _m (T _m ^{base mismatch} – T _m ^{base match}).

^c d(iC) = ^MeiC_d = 5-Methyl-2′-deoxyisocytidine. ^c X stands for the bases in the row (iG_d, 2a, 2b), Y for the bases in the line (iC, C, G, T, A).

^a K _TAUT = [keto]/[enol], measured in dioxane-water mixtures.