Abstract
We rank the reactivity of the adenyl residues (A) of model DNA and RNA molecules with electropositive subnano size [Ag] sites as a function of nucleic acid primary sequences and secondary structures and in the presence of biological amounts of Cl^−^ and Na^+^ or Mg^2+^ ions. In these conditions A is markedly more reactive than any other nucleic acid bases. A reactivity is higher in ribo (r) than in deoxyribo (d) species [pA > p__d__A and (pA)~n~ ≫ (p__d__A)~n~]. Base pairing decreases A reactivity in corresponding duplexes but much less in r than in d. In linear single and paired __d__CAG or __d__GAC loci, base stacking inhibits A reactivity even if A is bulged or mispaired (A^.^A). __d__A tracts are highly reactive only when dilution prevents self‐association and duplex structures. In d hairpins the solvent‐exposed A residues are reactive in CAG and GAC triloops and even more in ATC loops. Among the eight __r__G^1^N^2^R^3^A^4^ loops, those bearing a single A (A^4^) are the least reactive. The solvent‐exposed A^2^ is reactive, but synergistic structural transitions make the initially stacked A residues of any __r__GNAA loop much more reactive. Mg^2+^ cross‐bridging single strands via phosphates may screen A reactivity. In contrast d duplexes cross‐bridging enables “A flipping” much more in __r__A^.^U pairs than in __d__A^.^T. Mg^2+^ promotes A reactivity in unpaired strands. For hairpins Mg^2+^ binding stabilizes the stems, but according to A position in the loops, A reactivity may be abolished, reduced, or enhanced. It is emphasized that not only accessibility but also local flexibility, concerted docking, and cation and anion binding control A reactivity. © 2006 Wiley Periodicals, Inc. Biopolymers 82: 6–28, 2006
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