Identification and quantification of small organic molecules capable of binding to a protein of interest with reasonable affinity and specificity is a central problem. Via developing DNA-encoded recognizing probe, we validate a proof-of-principle for constructing of small target-to-DNA conversion that screens the small molecule-protein interaction. Successful identification of β-indole acetic acid, abscisic acid, or 2,4-dichlorophenoxyacetic acid/corresponding antibody binding implies its fascinating potential for interrogating small molecule/protein interaction.

A new strategy for one-step, reusable and sensitive detection of a single-base mutation based on an electrochemical molecular switch is developed in the present work. When the hybridization reaction takes place in the presence of target DNA, the Fc-labeled terminal of the open switch molecule can be captured by the probe through the predesigned complementary bases of both sequences. By this method, a signal-on sensor featuring both generalizability and simplicity towards reagentless detection of DNA with sensitivity and selectivity electrochemical system is built on. The approach had been demonstrated with the identification of a single-base mutation of alpha-thalassemia point mutation in Hb Constant Spring codon 142 (TAA --> CAA). The wild-type and mutant-type of the synthetic 16 mer DNA sequences as the model targets were successfully discriminated. The results showed that the response signal was linear to the logarithm of the target concentration in the range from 0.01 to 100 pM with a detection limit of 0.01 pM. The regeneration experiment demonstrated that the sensor interface can be easily and successfully regenerated. All these revealed that the present system is a promising candidate for single-base mutation discrimination.

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