Synthesis and Characterization of Reversible Covalent HDAC4 Inhibitors.

Methods Mol Biol

Department of Chemical Engineering and Biotechnology, University of Applied Sciences, Darmstadt, Germany.

Published: October 2022


Category Ranking

98%

Total Visits

921

Avg Visit Duration

2 minutes

Citations

20

Article 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.

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-1-0716-2788-4_14DOI Listing

Publication Analysis

Top Keywords

hdac4 inhibitors
8
covalent bond
8
synthesis characterization
4
characterization reversible
4
reversible covalent
4
covalent hdac4
4
inhibitors cyanoacrylates
4
cyanoacrylates define
4
define class
4
class inhibitors
4

Similar Publications

Cardiovascular disease (CVD) is a major global health threat, as its incidence and mortality rates continue to rise, highlighting the urgent need for effective therapeutic strategies. Histone deacetylase 4 (HDAC4), a member of class IIa HDACs, has attracted increasing attention in recent years for its role in CVD. Studies have shown that HDAC4 can influence the development and progression of CVD such as cardiac hypertrophy, hypertension and atherosclerosis by regulating key pathophysiological processes including inflammation, fibrosis and apoptosis.

View Article and Find Full Text PDF

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is associated with neurological symptoms, but the molecular mechanisms have not yet been identified. Since the S1 subunit (S1) of the envelope of the SARS-CoV2 Spike glycoprotein can reach the CNS, we studied whether S1 could cause neuronal death in a direct manner. Transfection of the S1 plasmid in SH-SY5Y cells reduces cell survival in a time-dependent manner, whereas the overexpression of the S2 subunit does not.

View Article and Find Full Text PDF

Epigenetic therapy and targeted protein degradation have converged in the development of histone deacetylases (HDACs)-targeting proteolysis-targeting chimeras (PROTACs), offering a novel approach to cancer treatment. Unlike traditional HDAC inhibitors, HDAC-PROTACs facilitate selective degradation of HDACs via the ubiquitin-proteasome system, effectively eliminating both enzymatic and scaffolding functions. These bifunctional molecules recruit HDACs to E3 ligases, triggering ubiquitination and subsequent proteasomal degradation.

View Article and Find Full Text PDF

Purpose: The purpose of this study was to investigate fibroblast markers and histone deacetylase (HDAC) 4 in orbital tissues and orbital fibroblasts from patients with Graves' ophthalmopathy (GO) and healthy controls.

Methods: Hematoxylin and eosin (H&E), Masson's trichrome, and Verhoeff's Van Gieson (VVG) staining were performed on GO and control orbital tissues. Immunohistochemistry on fibroblast markers were investigated.

View Article and Find Full Text PDF

Nucleocytoplasmic HDAC Inhibition Drives Acetylation-dependent TDP-43 Mislocalization and Disulfide-linked Oligomerization.

J Mol Biol

October 2025

Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea; Division of Bio-Medical Science & Technology, KIST School, University of Science and Technology (UST), Seoul 02792,Republic of Korea. Electronic address:

TDP-43 proteinopathies, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), are characterized by aberrant cytoplasmic mislocalization and aggregation of TDP-43. Here, we established a live-cell TDP43-BiFC model to visualize TDP-43 oligomerization in real time and screened diverse cellular stressors. Histone deacetylase (HDAC) inhibition emerged as the most potent trigger of TDP-43 oligomerization.

View Article and Find Full Text PDF