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

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Abstract

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.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant No. 81503463), the Science and Technology Planning Project of Taicang (TC2018JC04) and the Natural Science Research Projects of Universities in Jiangsu Province (Project No. 16KJB430037).

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Authors and Affiliations

  1. Department of Medical Science and Technology, Suzhou Chien-shiung Institute of Technology, Taicang, 215411, Jiangsu, China

    Xiangyang Miao, Yang Wang & Zhun Gu

  2. College of Medicine and Life Sciences, Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, China

    Xiangyang Miao, Dongsheng Mao & Limin Ning

  3. Center for Molecular Recognition and Biosensing, School of Life Sciences, Shanghai University, Shanghai, 200444, China

    Dongsheng Mao & Ya Cao

Authors
  1. Xiangyang Miao
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  2. Yang Wang
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  3. Zhun Gu
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  4. Dongsheng Mao
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  5. Limin Ning
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  6. Ya Cao
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Correspondence to Limin Ning or Ya Cao.

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Miao, X., Wang, Y., Gu, Z. et al. Cucurbit[8]uril-assisted peptide assembly for feasible electrochemical assay of histone acetyltransferase activity. Anal Bioanal Chem 411, 387–393 (2019). https://doi.org/10.1007/s00216-018-1445-4

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  • DOI: https://doi.org/10.1007/s00216-018-1445-4

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