Incorporation of a metal-mediated base pair into an ATP aptamer – using silver(I) ions to modulate aptamer function
Marius H. Heddinga, Jens Müller
Abstract
For the first time, a metal-mediated base pair has been used to modulate the affinity of an aptamer towards its target. In particular, two artificial imidazole 2'-deoxyribonucleosides (Im) were incorporated into various positions of an established ATP-binding aptamer (ATP, adenosine triphosphate), resulting in the formation of three aptamer derivatives bearing Im:Im mispairs with a reduced ATP affinity. A fluorescence spectroscopy assay and a binding assay with immobilized ATP were used to evaluate the aptamer derivatives. Upon the addition of one Ag(I) ion per mispair, stabilizing Im-Ag(I)-Im base pairs were formed. As a result, the affinity of the aptamer derivative towards ATP is restored again. The silver(I)-mediated base-pair formation was particularly suitable to modulate the aptamer function when the Im:Im mispairs (and hence the resulting metal-mediated base pairs) were located close to the ATP-binding pocket of the aptamer. Being able to trigger the aptamer function opens new possibilities for applications of oligonucleotides.