Boosting the specific molecular recognition of β-amyloid oligomer by constructing of antibody-mimic Y probe

The achievement of efficient structure-function unification involves the reasonable structure design of molecules and the application-oriented function regulation. DNA aptamer possesses feathers of high specificity, high stability, and easily flexible structure design, making it a promising candidate for access to specific functions. Inspired by the typical Y-shaped structure, a smart antibody-mimic Y probe (Y probe) composed of dual-aptamer recognition segments and rigid stem was designed for boosting the specific molecular recognition of β-amyloid oligomer (AβO). The spatial structure match of Y probe and AβO, as well as binding sites of AβO exposed to Y probe attributed to the enhanced specific targeting for AβO. As expected, Y probe specifically captured AβO but not Aβ monomer and fibril. For further investigation the reliability and applicability of Y probe, an electrochemical aptasensor based on Y probe was constructed and its performance was comprehensively tested. In particular, the aptasensor achieved a low limit of detection of 0.6 fM for AβO detection in a wide detection range (1 fM-5 nM). This work provided a universal method to promote specific interactions through the practical structure design of recognition molecules. Moreover, Y probe has positive implications for developing AβO biosensing platform in Alzheimer's disease early diagnosis.