Effective Modulation of DNA Duplex Stability by Reversible Transition Metal Complex Formation in the Minor Groove

Herein we describe the reversible changing of DNA duplex thermal stability by exploiting transition
metal complexation phenomena. A terpyridine ligand was conjugated to the N2‘-atoms of 2‘-amino-2‘-deoxyuridine and its locked counterpart 2‘-amino-LNA, and these metal-complexing monomers were
incorporated into oligodeoxyribonucleotides. Upon addition of varying amounts of transition metal ions, the
thermal stability of DNA duplexes containing these terpyridine-functionalized units in different constitutions
was affected to different degrees (ΔTm values = −15.5 to +49.0 °C, relative to the unmodified duplex).
The most pronounced effects were observed when two complexing monomers were positioned in opposite
strands. Addition of 1 equiv of Ni2+ to such a system induced extraordinary duplex stabilization. Molecular
modeling studies suggest, as an explanation for this phenomenon, formation of nickel-mediated interstrand
linkages in the minor groove. Addition of an excess of metal ions resulted in largely decreased Tm values.
Alternating addition of metal ions and EDTA demonstrated reversibility of metal ion-induced changes in
hybridization strength, proving that the described approach provides an efficient method for duplex stability
modulation.