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 via 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 Zn1 aptamer has little conformational change upon Zn2+ binding. The induced-fitting of the Co-1 aptamer and the lock-and-key binding of 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 Kd was determined to be 2.7 µM, whereas the Kd 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.