相关实验视频
Updated: Feb 14, 2026

09:11
Assays for Validating Histone Acetyltransferase Inhibitors
Published on: August 6, 2020
7.0K
通过辅酶A类似物抑制氨酸酸转移酶基因组的抑制
Faidra Voukia1, Nurgül Bilgin1, Steffen Bundgaard Andersen1
1Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark.
Molecules (Basel, Switzerland)
|February 13, 2026
概括
功能化协酶A类型被开发为强大的基因素酸转移酶 (KATs) 的抑制剂. 这些S-功能化辅酶A衍生物显示出创造针对KAT的化学探针的巨大潜力.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 希斯 lysine 乙化是真核生物中一个关键的翻译后修饰.
- 素乙转移酶 (KATs) 使用乙-辅酶A进行蛋白质乙化.
- 向KAT活性在生物医学上很重要,但基于乙-辅酶A的抑制剂设计尚未得到充分研究.
研究的目的:
- 设计和开发功能化的辅酶A类同类物作为人类KATs的抑制剂.
- 研究乙-辅酶A结构在制造强效和选择性KAT抑制剂方面的潜力.
主要方法:
- 合成功能化辅酶A类似物.
- 对人类KAT的抑制试验:GCN5,KAT8和HAT1.
- 确定未修改和修改的辅酶A类似物IC50值.
主要成果:
- 一个基替代的辅酶A模拟强烈抑制了GCN5 (IC50 = 10.9 μM) 和KAT8 (IC50 = 13.6 μM).
- 未修改的辅酶A是GCN5和KAT8 (IC50>150μM) 的一个弱抑制剂.
- 协酶A和一种用乙胺替代的模拟物有效抑制了HAT1 (IC50分别为7.3μM和3.9μM).
结论:
- S-功能化协酶A类型可以有效地和选择性地抑制人类的KATs.
- 已开发的类似物具有显著的潜力,可以作为生物医学上重要的KAT的化学探测器.
- 这项研究强调了乙-辅酶A支架对KAT抑制剂设计的有用性.
相关概念视频
Histone Modification
16.3K
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
16.3K
Histone Modification
4.6K
4.6K
Cofactors and Coenzymes
87.7K
Enzymes require additional components for proper function. There are two such classes of molecules: cofactors and coenzymes. Cofactors are metallic ions and coenzymes are non-protein organic molecules. Both of these types of helper molecule can be tightly bound to the enzyme or bound only when the substrate binds.
87.7K
Cofactors and Coenzymes
12.9K
Enzymes are proteins made of amino acids. The functional group of each constituent amino acid catalyzes a wide variety of chemical reactions via ionic interactions or acid-base reactions. However, amino acids cannot catalyze oxidation-reduction and group transfer reactions and need to be aided by non-protein components called cofactors. Cofactors are also referred to as the chemical teeth of an enzyme.
Cofactors can be metallic ions or organic molecules called coenzymes. These types of helper...
Cofactors can be metallic ions or organic molecules called coenzymes. These types of helper...
12.9K
Histone Variants at the Centromere
5.1K
Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3...
5.1K
Feedback Inhibition
57.3K
Biochemical reactions are occurring constantly in cells, converting starting substances to different products, usually with the help of enzymes that speed the reactions. Without enzymes, it would take far too long for most reactions to occur to be useful to the cell!
57.3K

