改进的核酸 (2'-脱氧) 转移酶最大限度地提高了酶的杂交性,同时保持了催化效率
Peijun Tang1, Greice M Zickuhr2, Alison L Dickson2
1School of Biology, Biomedical Sciences Research Complex, University of St Andrews, St Andrews, Fife KY16 9ST, United Kingdom.
ACS chemical biology
|October 18, 2025
概括
工程核酸2'-脱氧基转移酶 (NDT) 提供了合成多种核酸类型的生物催化剂解决方案,克服了抗病毒和抗癌药物开发的复杂化学合成挑战.
科学领域:
- 生物催化剂是一种生物催化剂.
- 酵素工程是什么? 酶工程是什么
- 药用化学 医学化学
背景情况:
- 核酸相似物是感染和癌症的重要治疗药物.
- 核类相应物的传统化学合成是复杂和低效的.
- 核二脱氧化转移酶 (NDT) 酶显示出生物催化剂的潜力.
研究的目的:
- 为了改造NDT酶以提高各种核化的催化效率.
- 扩大NDT酶的基质范围,以便更广泛地生产核酸类比物.
- 了解增强酶活性和基质特异性的分子基础.
主要方法:
- 合理的酶设计和NDT从*Chroococcidiopsis thermalis* (CtNDT) 和*Bacillus psychrosaccharolyticus* (BpNDT) 的突变发生.
- 工程酶变体的晶体结构的确定.
- 用各种核酸基质对酶变体的动态表征.
主要成果:
- 工程 NDT 变种表现出对核化物和3-脱氧核化物的增强催化效率.
- 催化效率的提高主要是由于营业额的增加.
- 酶保持了广泛的核杂性,使得100多种不同的核产物得以合成.
- 水晶结构揭示了对扩展基质范围的分子洞察力.
结论:
- 无核酸技术的合理工程提供了一个强大的生物催化平台,用于核酸类模拟合成.
- 开发的酶和反应条件为产生多种核酸产物提供了一种多功能方法.
- 这一战略通过简化对复杂核类同类物质的获取来促进新疗法的开发.
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
9.1K
10:24NMR-Based Activity Assays for Determining Compound Inhibition, IC50 Values, Artifactual Activity, and Whole-Cell Activity of Nucleoside Ribohydrolases
Published on: June 30, 2019
10.5K
相关概念视频
01:28Biosynthesis of Nucleic Acids
963
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...
963
02:36Transfer RNA Synthesis
13.2K
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...
13.2K
02:23RNA Editing
9.8K
RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
9.8K