Use of pK_a Differences To Enhance the Formation of Base Triplets Involving C−G and G−C Base Pairs

Abstract

Two C-nucleosides are employed for the recognition of dC-dG base pairs. Both derivatives are related to dC but lack the O2-carbonyl. The absence of the carbonyl should eliminate any unfavorable steric interactions at this site. One of the derivatives contains a 2-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 base 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. Triplex 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.

Reversed-phase separation methods for glycan analysis

“…In many of the methods using PA, a buffer was added to the solvents to maintain a low pH. As the p K a of PA is 6.8, the molecule is protonated at low pH [97]. Testa and Wild [98] showed that this protonation results in increased fluorescence.…”

Triple‐Helical Recognition of RNA Using 2‐Aminopyridine‐Modified PNA at Physiologically Relevant Conditions

“…[10] More recently, derivatives of 2-aminopyridine have been used to increase the stability of DNA triple helices at high pH. [11–14] Before our studies, this approach had not been used in PNA.…”

Effects of the minor groove pyrimidine nucleobase functional groups on the stability of duplex DNA: The impact of uncompensated minor groove amino groups

“…To prepare the desired DNA sequences, we needed to convert the nucleosides into appropriately protected phosphoramidite derivatives. Four of the nucleoside phosphoramidite derivatives were prepared as described previously 11, 21. The remaining two phosphoramidite derivatives (the C analogs with F or CH 3 replacing the O2‐carbonyl) were prepared from the parent nucleosides15 as described here.…”