Cucurbit[8]uril-assisted peptide assembly for feasible electrochemical assay of histone acetyltransferase activity

Accumulating findings demonstrate the importance of histone acetyltransferases (HATs) in regulating the acetylation of histones and reveal that their aberrant catalytic activities are involved in the occurrence and progress of numerous diseases. Herein, a feasible electrochemical method is proposed to assay the activity of HAT. The critical elements of the assay method are the hindrance of HAT-catalyzed acetylation against carboxypeptidase Y-catalyzed digestion and cucurbit[8]uril-assisted peptide assembly, which may recruit peptide-templated silver nanoparticles onto the electrode surface, producing significant electrochemical signals. Taking p300 as a model HAT, the assay method is validated to exhibit desirable selectivity, reproducibility, and usability in inhibitor analysis, and allow absolute activity determination in a linear range from 0.1 to 50 nM with a detection limit of 0.055 nM, which is lower than those of previous reports. Therefore, this work may provide an effective tool for HAT activity assay, which will be of great potential in HAT-related fundamental research, disease diagnosis, and drug development in the future. Graphical abstract ᅟ