Dual-Aptamer-Conjugated Molecular Modulator for Detecting Bioactive Metal Ions and Inhibiting Metal-Mediated Protein...

Bioactive metal ions play important roles in both physiological and pathological processes. Developing biosensing probes for bioactive metal ion detection can contribute to fields including disease diagnosis and therapy and studying the mechanisms of biological activities. In this work, we designed a dual-aptamer-conjugated molecular modulator that can detect Zn²⁺ and further inhibit Zn²⁺-induced amyloid β (Aβ) aggregation. The molecular modulator is able to selectively target Aβ species and block Zn²⁺ due to the specific recognition capability of aptamers. With the binding of Zn²⁺, the fluorescence signal of this molecular modulator is restored, thus allowing for Zn²⁺ detection. More importantly, this molecular modulator can inhibit the generation of Zn²⁺-triggered Aβ aggregates due to the trapping of Zn²⁺ around Aβ species. Circular dichroism measurements reveal that the dual-aptamer-conjugated molecular modulator prevents the conformational transition of the Aβ monomer from a random coil to a β-sheet. Furthermore, after treating with the molecular modulator, no Aβ aggregate is observed in the Aβ solution with added Zn²⁺, demonstrating that Aβ aggregation is successfully inhibited by this molecular modulator. Our approach provides a promising tool for detecting bioactive metal ions and studying the molecular mechanisms behind life activities.