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Hydroxamic acid-modified peptide microarrays for profiling isozyme-selective interactions and inhibition of histone deacetylases

Moreno-Yruela, C.; Bæk, M.; Vrsanova, Adela Eugenie; Schulte, C.; Maric, H. M.; Olsen, C. A.

Histones control gene expression by regulating chromatin structure and function. The posttranslational modifications (PTMs) on the side chains of histones form the epigenetic landscape, which is tightly controlled by epigenetic modulator enzymes and further recognized by so-called reader domains. Histone microarrays have been widely applied to investigate histone–reader interactions, but not the transient interactions of Zn$^{2+}$-dependent histone deacetylase (HDAC) eraser enzymes. Here, we synthesize hydroxamic acid-modified histone peptides and use them in femtomolar microarrays for the direct capture and detection of the four class I HDAC isozymes. Follow-up functional assays in solution provide insights into their suitability to discover HDAC substrates and inhibitors with nanomolar potency and activity in cellular assays. We conclude that similar hydroxamic acid-modified histone peptide microarrays and libraries could find broad application to identify class I HDAC isozyme-specific substrates and facilitate the development of isozyme-selective HDAC inhibitors and probes.

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Verlagsausgabe §
DOI: 10.5445/IR/1000129091
Veröffentlicht am 29.01.2021
DOI: 10.1038/s41467-020-20250-9
Zitationen: 1
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Angewandte Biowissenschaften (IAB)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2021
Sprache Englisch
Identifikator ISSN: 2041-1723
KITopen-ID: 1000129091
Erschienen in Nature Communications
Verlag Nature Research
Band 12
Heft 1
Seiten Art.-Nr.: 62
Schlagwörter array; chemical compound; enzyme; enzyme activity; gene expression; inhibition; inhibitor; peptide; protein
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