A general transition metal binding aptamer following the Irving–Williams series

Using both Co²⁺ and Ni²⁺ as target metal ions, aptamer selections were carried out by immobilization of a DNA library <i>via</i> hybridization. A set of aptamers were obtained although they all showed binding to both metal ions. The Co-1 aptamer was highly enriched in both selections and it is a general metal binding aptamer with binding affinity following the Irving-Williams series: Mn²⁺ < Fe²⁺ < Co²⁺ < Ni²⁺ < Cu²⁺ > Zn²⁺. Using NMR spectroscopy, Co-1 forms new base pairs with a relatively large structural change upon binding to Zn²⁺, whereas a previously reported Zn-1 aptamer shows less conformational change and rigidifies upon Zn²⁺ binding. The induced-fitting of the Co-1 aptamer and the lock-and-key binding of the Zn-1 aptamer may explain the general metal binding of the former. Using isothermal titration calorimetry, Co-1 binding Co²⁺ was an enthalpy-driven event and the <i>K</i> _d was determined to be 2.7 μM, whereas the <i>K</i> _d from the strand-displacement assay was 76 nM. The Co-1 aptamer is the first reported aptamer to follow the Irving-Williams series, although this series is very prevalent in proteins. This aptamer can thus serve as a model system for understanding metal binding by DNA and can also be a general first-row transition metal sensing element.