基于结构的低纳米O-GlcNAc转移酶抑制剂的演变
Sara E S Martin1, Zhi-Wei Tan1, Harri M Itkonen1
1Department of Microbiology , Harvard Medical School , Boston , Massachusetts 02115 , United States.
Journal of the American Chemical Society
|October 5, 2018
概括
研究人员开发了强大的细胞透性抑制剂,用于O结合的N- 乙糖胺转移酶 (OGT). 这些新型化合物向OGT
科学领域:
- 生物化学和分子生物学
- 酵素学
- 化学生物学
背景情况:
- 可逆蛋白质糖化是元动物的一个关键的调节过程.
- 与O结合的N-乙糖胺转移酶 (OGT) 催化了所有的核细胞质糖化.
- 开发有力的细胞透性OGT抑制剂对于生物研究至关重要.
研究的目的:
- 设计和合成新型,强效,细胞透的OGT抑制剂.
- 研究OGT抑制剂的结构活性关系.
- 提供关于抑制糖转移酶的见解.
主要方法:
- 基于结构的药物设计和OGT抑制剂的演变.
- 生物化学测试以确定抑制功效 (例如,低纳米范围).
- 细胞测定以确认目标活性和细胞透性.
主要成果:
- 基于结构的成功进化产生了具有低纳米分子功率的OGT抑制剂.
- 化合物表现出显著的目标细胞活性.
- 这项研究为OGT抑制提供了新的化学支架.
结论:
- 开发的抑制剂是研究OGT功能的有价值的工具.
- 这些发现提供了抑制一种具有挑战性的酶类型的新策略.
- 这项研究推进了与糖化相关过程的化学生物学和药物发现领域.
相关概念视频
The Evidence for Evolution
48.3K
Genetic variations accumulating within populations over generations give rise to biological evolution. Evolutionary changes can result in the formation of novel varieties and entire new species. These changes are responsible for the diverse forms of life inhabiting the planet. The evidence for evolution suggests that all living organisms descended from common ancestors.
48.3K
Convergent Evolution
33.0K
Evolution shapes the features of organisms over time, ensuring that they are suited for the environments in which they live. Sometimes, selection pressure leads to the rise of similar but unrelated adaptations in organisms with no recent common ancestors, a process known as convergent evolution.
33.0K
Eukaryotic Transcription Inhibitors
11.0K
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...
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
11.0K
Eukaryotic Evolution
41.6K
The endosymbiont theory is the most widely accepted theory of eukaryotic evolution; however, its progression is still somewhat debated. According to the nucleus-first hypothesis, the ancestral prokaryote first evolved a membrane to enclose DNA and form the nucleus. Conversely, the mitochondria-first hypothesis suggests that the nucleus was formed after endosymbiosis of mitochondria.
Contrary to the endosymbiont theory, the eukaryote-first hypothesis proposes that the simpler prokaryotic and...
Contrary to the endosymbiont theory, the eukaryote-first hypothesis proposes that the simpler prokaryotic and...
41.6K
Synteny and Evolution
3.8K
John H. Renwick first coined the term “synteny” in 1971, which refers to the genes present on the same chromosomes, even if they are not genetically linked. The species with common ancestry tend to show conserved syntenic regions. Therefore, the concept of synteny is nowadays used to describe the evolutionary relationship between species.
Around 80 million years ago, the human and mice lineages diverged from the common ancestor. During the course of evolution, the ancestral...
Around 80 million years ago, the human and mice lineages diverged from the common ancestor. During the course of evolution, the ancestral...
3.8K
Gene Evolution - Fast or Slow?
8.2K
The genomes of eukaryotes are punctuated by long stretches of sequence which do not code for proteins or RNAs. Although some of these regions do contain crucial regulatory sequences, the vast majority of this DNA serves no known function. Typically, these regions of the genome are the ones in which the fastest change, in evolutionary terms, is observed, because there is typically little to no selection pressure acting on these regions to preserve their sequences.
In contrast, regions which code...
In contrast, regions which code...
8.2K


