NICKEL-BASED PROBES OF NUCLEIC-ACID STRUCTURE BIND TO GUANINE N7 BUT DO NOT PERTURB A DYNAMIC EQUILIBRIUM OF EXTRAHELICAL GUANINE RESIDUES

Physical and chemical data are presented to resolve two important aspe cts of the mechanism and application of nucleic acid probes based on m acrocyclic complexes of nickel. Direct coordination between nickel and guanine N7 had previously been suggested by the probes' sensitivity t o the structural environment surrounding this nucleotide ligand. The f irst evidence for such recognition has now been obtained by a diagnost ic ability of certain nickel complexes to convert poly(dG-dC) from a B - to Z-helix. Interaction between these complexes and 5'-GMP was also monitored by H-1 NMR and found to be characteristic of ligation betwee n guanine N7 and nickel. Despite this mode of binding, the specificity of guanine oxidation reflects native conformations of DNA that are in dependent of nickel. To demonstrate this, the relative reactivity of e ach guanine forming an equilibrium of extrahelical bulges was shown he re to mimic the distribution of species determined by previous NMR stu dies in the absence of nickel. Accordingly, nickel reagents may now be applied with confidence when a number of dynamic features of nucleic acid structure are examined.