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.
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) = MeiCd = 5-Methyl-2′-deoxyisocytidine. c X stands for the bases in the row (iGd, 2a, 2b), Y for the bases in the line (iC, C, G, T, A).
a K TAUT = [keto]/[enol], measured in dioxane-water mixtures.