Direct Monitoring of Cytosine Protonation in an Intramolecular DNA Triple Helix

Molecular Basis of Perhydrolase Activity in Serine Hydrolases

“…Therefore, the significantly smaller magnitudes of Δ H and Δ S for Pyr15TM at pH 6.8 relative to those for Pyr15TM at pH 6.1 (Table 2) suggests that the triplex formation with Pyr15TM at pH 6.8 was significantly more substoichiometric than that with Pyr15TM at pH 6.1, which was also supported by the significantly smaller magnitudes of K a and Δ G for Pyr15TM at pH 6.8 (Table 2). In the substoichiometric triplex formation, the cytosine bases in the TFO may be protonated to a lesser extent, resulting in weaker hydrogen‐bonding interactions and possibly also weaker base‐stacking interactions 13. In contrast, the K a and Δ G for Pyr15TM at pH 6.1 and those for the 2′,4′‐BNA NC ‐modified TFOs at pH 6.8 were quite similar (Table 2), which suggests that the triplex formations under these conditions were similarly quite stoichiometric.…”

Differential reactivity of α and β 2′-deoxyribonucleosides towards protonation and metalation

“…Although the pK a values of the natural nucleobases are well outside the physiological pH region, rendering the corresponding nucleosides neutral under physiological conditions, numerous examples are known of nucleobases within longer DNA fragments showing unusual acidity constants. These examples include the protonated cytidine residue in CH + GC triple helices [2], in the i-motif [3], or acting as an acid-base catalyst in the self-splicing hepatitis delta virus ribozyme [4]. During our recently reported studies on artificial 2 0 -deoxyribonucleosides based on azoles [5], we observed a differential reactivity of the respective a and b nucleosides towards protonation despite the fact that they only differ by the configuration at one stereo center that is not even included in the protonation equilibrium.…”

Ligand‐pKa Shifts through Metals: Potential Relevance to Ribozyme Chemistry

“…The shifts in apparent pK a values can be quite substantial, e.g., from 4.5 in isolated CMP up to 9.5 in a triple-stranded DNA [28]. The difference in pK a (between apparent value and that of the free nucleotide) is a direct measure for the stability of the base-pair associate [29]. These shifts clearly exceed the normal sequencedependency of pK a values of a particular nucleotide within an oligonucleotide, which, in the case of GMP residues, are below 1 log unit in single-stranded DNA molecules [30], and which are attributed to a combination of electrostatic effects within the oligonucleotide.…”