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

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.