在mRNA显示中识别共价循环抑制剂
Sabrina E Iskandar1,2, Lilly F Chiou3,4, Tina M Leisner2
1Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, United States.
Journal of the American Chemical Society
|July 3, 2023
概括
我们开发了一种使用mRNA显示的新方法来发现共价抑制剂. 这种方法利用反应性脱氨酸来识别针对蛋白质相互作用的强抑制剂.
科学领域:
- 生物化学
- 化学生物学
- 药物发现
背景情况:
- 由于选方法有限,在共价抑制剂的发现中未得到充分利用.
- 共价抑制剂为蛋白质表面和接口提供独特的结合能力.
研究的目的:
- 开发一种使用mRNA显示识别共价循环抑制剂的方法.
- 确定脱氨酸 (Dhas) 作为对共价抑制的有效电友.
主要方法:
- 结合协同和后翻译库多样化以创建循环库.
- 将反应性脱氨酸 (Dhas) 纳入库.
- 使用mRNA显示对两个模型蛋白目标进行选择.
主要成果:
- 鉴定出具有低纳米分子活性的强共价循环抑制剂.
- 通过选择的抑制剂证明了蛋白质与蛋白质相互作用的破坏.
- 用于共价药物发现的有效电友.
结论:
- 建立了用于共价抑制剂发现的新型mRNA显示方法.
- 展示了促进图书馆发展的协同多样化策略.
- 突出了作为向蛋白界面的共价抑制剂的潜力.
相关概念视频
RNA Interference
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...
Inhibitors of Bacterial Protein Synthesis
Aminoglycosides constitute a highly potent class of bactericidal antibiotics that exert their antimicrobial effects by targeting the bacterial ribosome, specifically disrupting protein synthesis. These polycationic molecules consist of amino-modified sugars linked via glycosidic bonds to an aminocyclitol core such as 2-deoxystreptamine or streptamine. Their strong positive charges facilitate tight binding to the negatively charged phosphate backbone of ribosomal RNA (rRNA), primarily at the 16S...


