Anchor extension: a structure-guided approach to design cyclic peptides ...
2021年6月7日 · To test our approach using a well characterized model system, we design cyclic peptides that inhibit histone deacetylases 2 and 6 (HDAC2 and HDAC6) with enhanced potency compared to the original anchor (IC 50 values of 9.1 and 4.4 nM for the best binders compared to 5.4 and 0.6 µM for the anchor, respectively).
Discovery of Potent and Selective Histone Deacetylase Inhibitors …
In contrast, here we investigate a variety of side chain functionalities by designing and carrying out total solid-phase synthesis (SPS) of one-bead–one-compound libraries 68 of cyclic peptides for the purpose of inhibiting HDAC enzymes. The present study focuses on HDACs with potent deacetylase activity against histones and standard ...
The Histone Deacetylase Family: Structural Features and ... - MDPI
2024年5月10日 · Cyclic peptides, the most structurally intricate class of HDAC inhibitors, can be categorized into two groups based on the presence of the 2-amino-8-oxo-9, 10-epoxy-decanoyl (Aoe) moiety. In the first group, including cyclic peptides with the Aoe moiety, trapoxin A, trapoxin B and WF-3161 can be mentioned.
Peptide based macrocycles: selective histone deacetylase inhibitors ...
Each subtype of the Histone Deacetylase (HDAC) family perform a distinct role in the gene expression and cyclic peptides with their plentiful set of surface contacts, zinc binding group and macrocyclic cap, can target enzyme precisely through adequate modulation of the amino acid configurational and structural assortment.
Histone deacetylase function in CD4 + T cells - Nature
2018年7月18日 · HDAC inhibitors are grouped into four classes on the basis of their chemical structures: hydroxamates, short-chain fatty acids, benzamides and cyclic peptides 8.
HDAC Inhibitors: Innovative Strategies for Their Design and
2022年1月21日 · These favorable properties of 17 led the authors to propose these cyclic peptides as effective target-binding elements for PROTACs in general. Xiao et al. designed and synthesized selective HDAC3 degraders based on benzoylhydrazide inhibitors to recruit both CRBN and VHL E3 ligases [ 38 ].
From natural products to HDAC inhibitors: An overview of …
2021年12月15日 · To date, several HDAC inhibitors have been addressed for cancer therapy and they can be mainly divided into three types: hydroxymate, benzamide, and cyclic peptide. Vorinostat (SAHA) is a hydroxamic acid multi-HDAC inhibitor that blocks the enzymatic activity of both Class I (HDAC1, −2, and −3) and Class II (HDAC6) HDACs at low nanomolar ...
Histone deacetylase (HDACs) inhibitors: Clinical applications
2023年1月1日 · Cyclic tetrapeptide HDACi includes depsipeptides (romidepsin) and trapoxin. Romidepsin has been approved by FDA (2009) and EMA (European Medicines Agency) to treat CTCL, and it inhibits class I HDACs.
Hydroxamic Acid-Containing Peptides in the Study of Histone ...
2019年11月28日 · Histone deacetylases (HDACs) are ubiquitous enzymes that remove ε- N -acetyl-lysine posttranslational modifications (PTMs) on histone tails. The resulting PTM landscape affects chromatin packing and recruitment of transcription factors, in turn playing an indirect role in regulation of gene expression.
The emerging roles of HDACs and their therapeutic implications in ...
2022年9月15日 · HDACi treatment exerts antitumor effects by inducing cell cycle arrest, apoptosis, differentiation, and immunity in cancer cells (Falkenberg and Johnstone, 2014). HDACis can induce the expression of pro-apoptotic genes and proteins, leading to differentiation or cell cycle arrest (Suraweera et al., 2018).