一个用于核类模拟合成的统一平台
Matthew J Anketell1, Ethan Fung1, Wenbin Liu2
1Department of Chemistry, Simon Fraser University, Burnaby, BC, Canada.
概括
一种新的光氧合方法使得核酸相似物 (NA) 的高通量合成成为可能,用于药物发现. 这种灵活的平台产生了多样化的NA库,产生了具有抗HIV-1活性的化合物.
科学领域:
- 药用化学 医学化学
- 有机合成 有机合成
- 药物发现 药物发现 药物发现
背景情况:
- 核类型 (NA) 对于抗病毒和抗癌治疗至关重要.
- 目前的合成方法耗时且缺乏灵活性,限制了NA化学空间的探索.
- 开发高效,高通量NA合成对于发现新疗法至关重要.
研究的目的:
- 开发一个灵活和高效的平台,用于高吞吐量合成核酸相似物 (NA).
- 为了使药物发现的各种NA图书馆的生产.
- 识别具有潜在治疗应用的新型NA化合物.
主要方法:
- 在NA合成中使用光氧合策略.
- 开发了一种可扩展的中间体,用于合成各种NA类,包括C和N链接的NA.
- 应用了这个平台来生成一个多样化的核酸相似物库.
主要成果:
- 成功合成了C和N结合的核酸相似物.
- 从单个中间体中统一合成不同的NA类 (4'-thio,4'-imino,ProTides).
- 从合成的库中确定了几种具有显著抗HIV-1活性的打击化合物.
结论:
- 报道的光氧合平台为高通量NA合成提供了强大而高效的方法.
- 这种方法显著扩大了核酸相似物可访问的化学空间.
- 该平台预计将加速抗病毒和抗癌疗法的药物发现工作.
更多相关视频
08:46Regioselective O-Glycosylation of Nucleosides via the Temporary 2',3'-Diol Protection by a Boronic Ester for the Synthesis of Disaccharide Nucleosides
Published on: July 26, 2018
9.2K
11:37Protocol for the Solid-phase Synthesis of Oligomers of RNA Containing a 2'-O-thiophenylmethyl Modification and Characterization via Circular Dichroism
Published on: July 28, 2017
19.9K
相关概念视频
Biosynthesis of Nucleic Acids
1.4K
Nucleic acid biosynthesis is a fundamental biochemical process that produces the purine and pyrimidine nucleotides essential for DNA and RNA synthesis. This pathway maintains a balanced nucleotide pool, preventing imbalances that could jeopardize genetic integrity and cellular function. Given the crucial role of nucleotides, their synthesis is tightly regulated to ensure proper cellular homeostasis.Purine BiosynthesisThe biosynthesis of purine nucleotides begins with ribose-5-phosphate, a...
1.4K
Biosynthesis of Polysaccharides
816
Polysaccharides such as glycogen and starch are synthesized from nucleoside diphosphate sugars, primarily uridine diphosphate glucose (UDPG) and adenosine diphosphate glucose (ADPG). These activated glucose donors act as key intermediates in carbohydrate metabolism and biosynthesis. UDPG primarily involves glycogen synthesis in animals and many bacteria, while ADPG plays a fundamental role in starch synthesis in plants and certain bacteria.UDPG is formed when glucose-1-phosphate reacts with...
816
Nucleic Acids and Nucleotides
15.7K
Nucleic acids are the most important macromolecules for the continuity of life. They carry the cell's genetic blueprint and have instructions for its functioning. The two main types of nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA).
Deoxyribonucleic Acid (DNA)
DNA is the genetic material in all living organisms, ranging from single-celled bacteria to multicellular mammals. It is in the nucleus of eukaryotes and the organelles such as chloroplasts and mitochondria....
Deoxyribonucleic Acid (DNA)
DNA is the genetic material in all living organisms, ranging from single-celled bacteria to multicellular mammals. It is in the nucleus of eukaryotes and the organelles such as chloroplasts and mitochondria....
15.7K
Nucleic Acid Structure
9.8K
The pentose sugar in DNA is deoxyribose, while in RNA the pentose sugar is ribose. The difference between the sugars is the presence of the hydroxyl group on the ribose's second carbon and a hydrogen on the deoxyribose's second carbon. The phosphate residue attaches to the hydroxyl group of the 5′ carbon of one sugar and the hydroxyl group of the 3′ carbon of the sugar of the next nucleotide, which forms a 5′ to 3′ phosphodiester linkage.
DNA Structure
DNA...
DNA Structure
DNA...
9.8K
ATP and Macromolecule Synthesis
7.1K
Biological macromolecules are organic compounds, predominantly composed of carbon atoms. The carbon atoms are covalently bonded with hydrogen, oxygen, nitrogen, and other minor elements. There are four major biological macromolecule classes: carbohydrates, lipids, proteins, and nucleic acids.
Most macromolecules are composed of single subunits, or building blocks, called monomers. The monomers combine with each other using covalent bonds to form larger molecules known as polymers.
Conversion of...
Most macromolecules are composed of single subunits, or building blocks, called monomers. The monomers combine with each other using covalent bonds to form larger molecules known as polymers.
Conversion of...
7.1K
Nucleic acids
195.7K
Nucleic acids are the most important macromolecules for the continuity of life. They carry the cell's genetic blueprint and carry instructions for its functioning.
DNA and RNA
The two main types of nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). DNA is the genetic material in all living organisms, ranging from single-celled bacteria to multicellular mammals. It is in the nucleus of eukaryotes and in the organelles, chloroplasts, and mitochondria. In prokaryotes,...
DNA and RNA
The two main types of nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). DNA is the genetic material in all living organisms, ranging from single-celled bacteria to multicellular mammals. It is in the nucleus of eukaryotes and in the organelles, chloroplasts, and mitochondria. In prokaryotes,...
195.7K
