Synthesis and Characterization of Reversible Covalent HDAC4 Inhibitors

Anton Frühauf; Benjamin Wolff; Markus Schweipert; Franz-Josef Meyer-Almes

doi:10.1007/978-1-0716-2788-4_14

Synthesis and Characterization of Reversible Covalent HDAC4 Inhibitors

Methods Mol Biol. 2023:2589:207-221. doi: 10.1007/978-1-0716-2788-4_14.

Authors

Anton Frühauf¹, Benjamin Wolff¹, Markus Schweipert¹, Franz-Josef Meyer-Almes²

Affiliations

¹ Department of Chemical Engineering and Biotechnology, University of Applied Sciences, Darmstadt, Germany.
² Department of Chemical Engineering and Biotechnology, University of Applied Sciences, Darmstadt, Germany. franz-josef.meyer-almes@h-da.de.

PMID: 36255627
DOI: 10.1007/978-1-0716-2788-4_14

Abstract

Cyanoacrylates define a class of inhibitors which are capable to form a transient covalent bond with a cysteine flanking the binding site, thereby increasing the residence time and prolonging the inhibitory effect on the target protein under nonequilibrium conditions. Herein, we describe the synthetic access to cyanoacrylate-based HDAC4 inhibitors and the procedures for the characterization of the transient nature of the covalent bond between cyanoacrylates and thiols or cysteines in HDAC4.

Keywords: HDAC4; Histone deacetylase inhibitor; Residence time; Reversibility assays; Reversible covalent inhibitors.

MeSH terms

Binding Sites
Cyanoacrylates*
Cysteine* / metabolism
Histone Deacetylase Inhibitors / chemistry
Histone Deacetylase Inhibitors / pharmacology

Substances

Cysteine
Cyanoacrylates
Histone Deacetylase Inhibitors