具有多种化学功能的三核酸酸的合成和聚合酶识别
Journal of the American Chemical Society
|October 12, 2021
概括
研究人员合成了具有多种功能组的新型非天然遗传聚合物 (XNA),以提高治疗性体稳定性和结合性. 一个实验室进化的聚合酶识别了这些修饰的核酸三酸盐, 扩大了合成生物学能力.
科学领域:
- 合成生物学
- 生物化学
- 医学化学
背景情况:
- 非天然基因聚合物 (XNA) 由于其增强的稳定性而具有治疗潜力.
- 扩大XNA的化学多样性对于开发高亲和度的体来说至关重要.
- 目前的XNA合成方法需要进一步的化学多样化.
研究的目的:
- 合成和描述具有多种C-5功能组的新型α-l-threofuranosyl尿素三酸盐 (tUTP) 类似物.
- 评估这些修饰的tUTPs的聚合酶识别和纳入XNA聚合物.
- 阐明已修改的XNA基质的聚合酶识别的结构基础.
主要方法:
- 10种不同的C-5修饰的tUTP类似物的化学合成.
- 通过实验室开发的聚合酶 Kod-RSGA 评估基质识别.
- 确定Kod-RSGA后催化复合物的高分辨率X射线晶体结构.
主要成果:
- 成功合成了10种化学多样化的C-5改性tUTP基质.
- 通过Kod-RSGA对所有测试的tUTP类似物进行普遍识别和高效聚合.
- 通过X射线结晶学检测出一个大型的酶活性部位腔,其中包含多种C-5侧链.
结论:
- 这项研究提供了一种合成途径来扩大可进化的XNA系统的化学空间.
- 可以通过增强多样性的功能组实现统一的修改.
- 这些发现为具有更好的结合性和稳定性的新型治疗体铺平了道路.
相关概念视频
Nucleic Acid Structure
7.6K
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...
7.6K
ATP and Macromolecule Synthesis
6.3K
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...
6.3K
Phosphodiester Linkages
105.4K
Overview
Phosphodiester bond forms when a phosphoric acid molecule (H3PO4) links with two hydroxyl groups (–OH) of two other molecules, forming two ester bonds. Two water molecules are released in this process. The phosphodiester bond is commonly found in nucleic acids (DNA and RNA) and plays a critical role in their structure and function.
Phosphodiester Bonds Link Nucleotides Together
DNA and RNA are polynucleotides or long chains of nucleotides that are linked together. A nucleotide is...
Phosphodiester bond forms when a phosphoric acid molecule (H3PO4) links with two hydroxyl groups (–OH) of two other molecules, forming two ester bonds. Two water molecules are released in this process. The phosphodiester bond is commonly found in nucleic acids (DNA and RNA) and plays a critical role in their structure and function.
Phosphodiester Bonds Link Nucleotides Together
DNA and RNA are polynucleotides or long chains of nucleotides that are linked together. A nucleotide is...
105.4K
Transfer RNA Synthesis
12.4K
One of the unique features of tRNA is the presence of modified bases. In some tRNAs, modified bases account for nearly 20% of the total bases in the molecule. Altogether, these unusual bases protect the tRNA from enzymatic degradation by RNases.
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
12.4K
Biosynthesis of Nucleic Acids
328
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...
328
Nucleic Acids
46.9K
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,...
46.9K


