Coenzyme A-aptamer-facilitated label-free electrochemical stripping strategy for sensitive detection of histone acetyltransferase activity

Abnormal histone acetyltransferases (HAT) activity gives rise to all kinds of cellular diseases. Herein, we first report a coenzyme A (CoA)-aptamer-facilitated label-free electrochemical stripping biosensor for sensitive detection of HAT activity via square wave voltammetry (SWV) technique. The presence of HAT can lead to the transfer of the acetyl group from acetyl coenzyme A (Ac-CoA) to lysine residues of substrate peptide, thus generating CoA molecule. Later, CoA, which acts as an initiator, can embrace its aptamer via the typical target-aptamer interaction, then arousing deoxynucleotide terminal transferase (TdT)-induced silver nanoclusters (AgNCs) as signal output. Under optimized conditions, the resultant aptasensor shows obvious electrochemical stripping signal and is employed for HAT p300 analysis in a wide concentration range from 0.01 to 100 nM with a very low detection limit of 0.0028 nM (3δ/slope). The good analytical performances of the biosensor depend on the strong interaction of CoA and its aptamer and abundant stripping resource rooted from AgNCs. Next, the proposed biosensor is used for screening HAT's inhibitors and the practical HAT detection with satisfactory results. Therefore, the new, simple and sensitive HAT biosensor presents a promising direction for HAT-targeted drug discovery and epigenetic research.