Controlling a Chemical Reaction with an Aptamer

Abstract

Like enzymes, aptamers provide structurally‐defined binding pockets to hold their target molecules tightly. Unlike ribozymes, aptamers are not catalytic but could be applied to slowing down the rates of reactions that occur spontaneously in an aqueous environment. Examples of such chemical reactions might be the many oxidative reactions that are involved in inflammation, aging and cancer. To suppress such reactions, an aptamer needs to prevent access to or reactivity of the target molecule with very small oxidative species. We demonstrate that a model reaction, decolorization of malachite green (MG) by hydroxyl ions, can be regulated by the interaction of MG with the MG aptamer (MGA). That the effect of the MGA on the rate of MG decolorization is due to the structure of the MGA binding pocket is demonstrated by reversal of the effect by an antisense oligonucleotide to MGA. UV spectroscopy and stop‐flow analysis were used to study the kinetics of MGA suppression of MG decolorization of the MG‐MGA interaction. The 20 min half life of MG decolorization was reduced to almost infinite with a 3‐fold excess of MGA. The half‐life of the MG‐MGA interaction was 1.7 sec. The results show that an aptamer can be used to suppress a spontaneous chemical reaction and that this suppression can be readily controlled by an antisense oligonucleotide. Funded by the DOE under contract W‐7405‐Eng‐82 with the Ames National Laboratories.