Nickel-mediated allosteric manipulation of G-quadruplex DNAzyme for highly selective detection of histidine

Since abnormal metabolism of histidine (His) is defined as an indicator of several diseases, detection of His in biological fluids becomes increasingly urgent to us. However, due to similar structures and properties of different amino acids, selective quantification of His is difficulty, and typically needs the participation of special reagents. In this work, we report for the first time that nickel ions (Ni²⁺) can induce the allostery of G-quadruplex, and is thus able to manipulate the activity of G-quadruplex DNAzyme. Experimental results indicate the interaction between Ni²⁺ and guanine is critical to the allostery. In comparison with Ni²⁺-guanine interaction, Ni²⁺-His interaction exhibits higher affinity. Therefore, a colorimetric His biosensor is fabricated, and His can be facilely discriminated by naked eyes. Relying on the high activity of DNAzyme, His in a range of 50 nM-400 μM is determined with this method, and low detection limit (36 nM) is obtained. More importantly, His can be directly distinguished in the absence of other toxic reagents. In addition, the amount of His in serum is also measured, suggesting the applicability of this biosensor in real sample detection. Overall, this work provides an alternative way to design G-quadruplex DNAzyme-based analytical approaches.