--- _id: '9018' abstract: - lang: eng text: Anti-silencing function 1 (ASF1) is a conserved H3-H4 histone chaperone involved in histone dynamics during replication, transcription, and DNA repair. Overexpressed in proliferating tissues including many tumors, ASF1 has emerged as a promising therapeutic target. Here, we combine structural, computational, and biochemical approaches to design peptides that inhibit the ASF1-histone interaction. Starting from the structure of the human ASF1-histone complex, we developed a rational design strategy combining epitope tethering and optimization of interface contacts to identify a potent peptide inhibitor with a dissociation constant of 3 nM. When introduced into cultured cells, the inhibitors impair cell proliferation, perturb cell-cycle progression, and reduce cell migration and invasion in a manner commensurate with their affinity for ASF1. Finally, we find that direct injection of the most potent ASF1 peptide inhibitor in mouse allografts reduces tumor growth. Our results open new avenues to use ASF1 inhibitors as promising leads for cancer therapy. article_processing_charge: No article_type: original author: - first_name: May M full_name: Bakail, May M id: FB3C3F8E-522F-11EA-B186-22963DDC885E last_name: Bakail orcid: 0000-0002-9592-1587 - first_name: Albane full_name: Gaubert, Albane last_name: Gaubert - first_name: Jessica full_name: Andreani, Jessica last_name: Andreani - first_name: Gwenaëlle full_name: Moal, Gwenaëlle last_name: Moal - first_name: Guillaume full_name: Pinna, Guillaume last_name: Pinna - first_name: Ekaterina full_name: Boyarchuk, Ekaterina last_name: Boyarchuk - first_name: Marie-Cécile full_name: Gaillard, Marie-Cécile last_name: Gaillard - first_name: Regis full_name: Courbeyrette, Regis last_name: Courbeyrette - first_name: Carl full_name: Mann, Carl last_name: Mann - first_name: Jean-Yves full_name: Thuret, Jean-Yves last_name: Thuret - first_name: Bérengère full_name: Guichard, Bérengère last_name: Guichard - first_name: Brice full_name: Murciano, Brice last_name: Murciano - first_name: Nicolas full_name: Richet, Nicolas last_name: Richet - first_name: Adeline full_name: Poitou, Adeline last_name: Poitou - first_name: Claire full_name: Frederic, Claire last_name: Frederic - first_name: Marie-Hélène full_name: Le Du, Marie-Hélène last_name: Le Du - first_name: Morgane full_name: Agez, Morgane last_name: Agez - first_name: Caroline full_name: Roelants, Caroline last_name: Roelants - first_name: Zachary A. full_name: Gurard-Levin, Zachary A. last_name: Gurard-Levin - first_name: Geneviève full_name: Almouzni, Geneviève last_name: Almouzni - first_name: Nadia full_name: Cherradi, Nadia last_name: Cherradi - first_name: Raphael full_name: Guerois, Raphael last_name: Guerois - first_name: Françoise full_name: Ochsenbein, Françoise last_name: Ochsenbein citation: ama: Bakail MM, Gaubert A, Andreani J, et al. Design on a rational basis of high-affinity peptides inhibiting the histone chaperone ASF1. Cell Chemical Biology. 2019;26(11):1573-1585.e10. doi:10.1016/j.chembiol.2019.09.002 apa: Bakail, M. M., Gaubert, A., Andreani, J., Moal, G., Pinna, G., Boyarchuk, E., … Ochsenbein, F. (2019). Design on a rational basis of high-affinity peptides inhibiting the histone chaperone ASF1. Cell Chemical Biology. Elsevier. https://doi.org/10.1016/j.chembiol.2019.09.002 chicago: Bakail, May M, Albane Gaubert, Jessica Andreani, Gwenaëlle Moal, Guillaume Pinna, Ekaterina Boyarchuk, Marie-Cécile Gaillard, et al. “Design on a Rational Basis of High-Affinity Peptides Inhibiting the Histone Chaperone ASF1.” Cell Chemical Biology. Elsevier, 2019. https://doi.org/10.1016/j.chembiol.2019.09.002. ieee: M. M. Bakail et al., “Design on a rational basis of high-affinity peptides inhibiting the histone chaperone ASF1,” Cell Chemical Biology, vol. 26, no. 11. Elsevier, p. 1573–1585.e10, 2019. ista: Bakail MM, Gaubert A, Andreani J, Moal G, Pinna G, Boyarchuk E, Gaillard M-C, Courbeyrette R, Mann C, Thuret J-Y, Guichard B, Murciano B, Richet N, Poitou A, Frederic C, Le Du M-H, Agez M, Roelants C, Gurard-Levin ZA, Almouzni G, Cherradi N, Guerois R, Ochsenbein F. 2019. Design on a rational basis of high-affinity peptides inhibiting the histone chaperone ASF1. Cell Chemical Biology. 26(11), 1573–1585.e10. mla: Bakail, May M., et al. “Design on a Rational Basis of High-Affinity Peptides Inhibiting the Histone Chaperone ASF1.” Cell Chemical Biology, vol. 26, no. 11, Elsevier, 2019, p. 1573–1585.e10, doi:10.1016/j.chembiol.2019.09.002. short: M.M. Bakail, A. Gaubert, J. Andreani, G. Moal, G. Pinna, E. Boyarchuk, M.-C. Gaillard, R. Courbeyrette, C. Mann, J.-Y. Thuret, B. Guichard, B. Murciano, N. Richet, A. Poitou, C. Frederic, M.-H. Le Du, M. Agez, C. Roelants, Z.A. Gurard-Levin, G. Almouzni, N. Cherradi, R. Guerois, F. Ochsenbein, Cell Chemical Biology 26 (2019) 1573–1585.e10. date_created: 2021-01-19T11:04:50Z date_published: 2019-11-21T00:00:00Z date_updated: 2023-02-23T13:46:53Z day: '21' doi: 10.1016/j.chembiol.2019.09.002 extern: '1' external_id: pmid: - '31543461' intvolume: ' 26' issue: '11' keyword: - Clinical Biochemistry - Molecular Medicine - Biochemistry - Molecular Biology - Pharmacology - Drug Discovery language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1016/j.chembiol.2019.09.002 month: '11' oa: 1 oa_version: Published Version page: 1573-1585.e10 pmid: 1 publication: Cell Chemical Biology publication_identifier: issn: - 2451-9456 publication_status: published publisher: Elsevier quality_controlled: '1' status: public title: Design on a rational basis of high-affinity peptides inhibiting the histone chaperone ASF1 type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 26 year: '2019' ...