相关实验视频
Updated: Jul 16, 2026

09:11
Assays for Validating Histone Acetyltransferase Inhibitors
Published on: August 6, 2020
对阿祖胺和基因脱乙酶抑制活性的分子洞察力
Nakia Maulucci1, Maria Giovanna Chini, Simone Di Micco
1Department of Chemistry, University of Salerno, Via Ponte Don Melillo, 84084 Fisciano, Salerno, Italy.
Journal of the American Chemical Society
|February 22, 2007
概括
阿祖胺E是一种强有力的基因素脱乙酶 (HDAC) 抑制剂,通过合成变体进行了研究,以了解其活性和结合. 这项研究有助于设计用于癌症治疗的新型HDAC抑制剂.
科学领域:
- 自然产品化学 自然产品化学
- 药用化学 医学化学
- 生物化学 生物化学
背景情况:
- 阿祖胺E是一种来自Mycale izuensis的循环四,是一种强大的天然基因素脱乙酶 (HDAC) 抑制剂.
- 了解HDAC抑制剂的结构-活性关系对于开发新的癌症疗法至关重要.
研究的目的:
- 合成和评估阿祖胺E的立体化学变体,以阐明侧链拓在HDAC抑制中的作用.
- 为了确定azumamides和基因素脱乙酶样蛋白 (HDLP) 模型受体之间的结合相互作用.
- 调查阿祖胺E对不同基因素脱乙酶 (HDAC) 亚型的异型选择性.
主要方法:
- 阿祖胺E立体化学变体的化学合成.
- 对HDAC抑制活性的评估.
- 用HDLP受体模型进行分子建模和对接研究.
主要成果:
- 立体化学变异证实了侧链拓对HDAC抑制功能的影响.
- 阐明了阿祖胺和HDLP模型受体之间的识别模式.
- 阿祖胺E在HDAC类亚型中表现出前所未有的异型选择性.
结论:
- 在受体结合口袋内建立了阿祖胺-HDLP相互作用的可信模型.
- 这项研究为新型循环四基HDAC抑制剂的合理设计提供了框架.
- 这些发现支持了阿祖马胺作为抗瘤剂的潜力.
相关概念视频
Spreading of Chromatin Modifications
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer is an enzyme that can...
Writers
The writer is an enzyme that can...
Histone Modification
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 deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Histone Modification
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 deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Eukaryotic Transcription Inhibitors
Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a DNA...
Eukaryotic transcription inhibitors usually contain two distinct domains, a DNA...
Histone Variants at the Centromere
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 variants are also...
Inhibitors of Bacterial DNA Synthesis
Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These antibiotics are selectively...

