稳定性伪uridimycin:合成,RNA聚合酶抑制活性,和抗菌活性的二基改性类似物
Avraz F Anwar1, Christopher F Cain1, Michael J Garza1
1Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, 46556, USA.
ChemMedChem
|September 26, 2023
概括
合成了化学稳定型伪乌里迪米辛 (PUM) 的类似物,以提高稳定性. 这些修改后的PUM化合物保留了抗菌活性,为现有的RNA聚合酶抑制剂提供了有希望的替代品.
科学领域:
- 微生物学 微生物学
- 药用化学 医学化学
- 分子生物学分子生物学
背景情况:
- 伪uridimycin (PUM) 是一种针对细菌RNA聚合酶 (RNAP) 的C核二抗生素.
- 与目前的RNAP抑制剂相比,PUM表现出较低的自发抵抗率.
- 的临床实用性受到其在水溶液中的不稳定性所限制.
研究的目的:
- 合成化学稳定PUM的类似物.
- 评估这些类型的RNAP抑制和抗菌活性.
- 为了确定增强PUM稳定性的修改,而不会影响疗效.
主要方法:
- 具有修改链接的PUM类似物的化学合成.
- 对RNAP抑制的评估.
- 对抗相关病原体的抗菌活性的评估.
- 在水性缓冲器中分析化合物稳定性.
主要成果:
- 有针对性的修改成功缓解了胺酸键裂变,增强了PUM稳定性.
- 含有胺或化异的类型保留了显著的抗菌活性.
- 在稳定类型中保持了RNAP抑制.
结论:
- 化学稳定的PUM类似物提供了更好的稳定性,并保持了强大的抗菌活性.
- 这些类似物代表了一种有前途的新型抗生素类别,针对细菌RNAP.
- 进一步开发可能会导致具有降低抗性潜力的新疗法.
更多相关视频
09:04Sequence-specific and Selective Recognition of Double-stranded RNAs over Single-stranded RNAs by Chemically Modified Peptide Nucleic Acids
Published on: September 21, 2017
9.6K
11:56Antimicrobial Peptides Produced by Selective Pressure Incorporation of Non-canonical Amino Acids
Published on: May 4, 2018
12.5K
相关概念视频
Types of RNA
63.9K
Overview
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...
63.9K
RNA Stability
33.6K
Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
33.6K
Biosynthesis of Nucleic Acids
67
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...
67
Gene Regulation in Microbial Communities: Quorum Sensing
35
Quorum sensing is a mechanism of bacterial communication that enables coordinated gene expression in response to changes in population density. This facilitates collective behaviors that enhance survival, resource acquisition, and ecological adaptation. This process relies on small signaling molecules called autoinducers that accumulate as bacterial populations grow. When a critical threshold concentration of autoinducers is reached, bacterial cells collectively modify gene expression,...
35
RNA Interference
26.1K
RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
26.1K
Experimental RNAi
6.2K
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
6.2K
