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Updated: Jan 19, 2026
Assays for Validating Histone Acetyltransferase Inhibitors
Published on: August 6, 2020
Design on a Rational Basis of High-Affinity Peptides Inhibiting the Histone Chaperone ASF1
May Bakail1, Albane Gaubert2, Jessica Andreani1
1Institute Joliot, Commissariat à l'énergie Atomique (CEA), Direction de la Recherche Fondamentale (DRF), 91191 Gif-sur-Yvette, France; Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ. Paris-Sud, Université Paris-Saclay, 91198 Gif-sur-Yvette Cedex, France.
Researchers designed potent peptide inhibitors targeting Anti-silencing function 1 (ASF1) to combat cancer. These ASF1 inhibitors demonstrated significant tumor growth reduction in preclinical models, offering a promising new therapeutic strategy.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Anti-silencing function 1 (ASF1) is a histone chaperone crucial for DNA processes.
- ASF1 is overexpressed in tumors, making it a potential therapeutic target for cancer treatment.
Purpose of the Study:
- To design and validate peptide inhibitors targeting the ASF1-histone interaction.
- To evaluate the therapeutic potential of ASF1 inhibitors in cancer models.
Main Methods:
- Utilized structural, computational, and biochemical methods for rational peptide design.
- Employed epitope tethering and interface contact optimization to create potent inhibitors.
- Assessed inhibitor efficacy in cultured cells and in mouse allograft tumor models.
Main Results:
- Identified a highly potent ASF1 peptide inhibitor with a 3 nM dissociation constant.
- Demonstrated that ASF1 inhibitors impair cancer cell proliferation, cell-cycle progression, migration, and invasion.
- Showed that direct injection of ASF1 peptide inhibitors reduces tumor growth in mouse models.
Conclusions:
- Developed effective peptide inhibitors targeting the ASF1-histone interaction.
- Validated ASF1 inhibitors as a promising therapeutic strategy for cancer therapy.
- Opened new avenues for developing ASF1-based cancer treatments.
