对N-甲基的核糖体合成
Alexander O Subtelny1, Matthew C T Hartman, Jack W Szostak
1Howard Hughes Medical Institute and Center for Computational and Integrative Biology, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA.
Journal of the American Chemical Society
|April 12, 2008
概括
这项研究表明,N-甲基氨基酸 (N-Me AAs) 可以使用复制的细菌翻译系统将其纳入中. 这一进步使得创建新的类图书馆用于药物发现成为可能.
科学领域:
- 生物化学 生物化学
- 合成生物学 合成生物学
- 药用化学 医学化学
背景情况:
- N-甲基氨基酸 (N-Me AAs) 是非核糖体 (NRPs) 的关键组成部分,是许多治疗药物的来源.
- N-Me AAs 增强类特性,如刚性,膜透性和蛋白酶抵抗性.
- 这些改性氨基酸对于合成具有治疗潜力的非自然具有价值.
研究的目的:
- 研究N-甲基氨基酸 (N-Me AAs) 在核糖体中被纳入的过程.
- 探索含有多个N-Me AAs的的合成,用于药物发现应用.
主要方法:
- 使用了复制的大肠杆菌翻译系统.
- 补充了化学甲基化,特别是氨基化总tRNA的系统.
- 识别了N-Me Leu,N-Me Thr和N-Me Val,以实现有效的核糖体结合.
主要成果:
- 通过核糖体有效地将三个特定的N-Me AAs (N-Me Leu,N-Me Thr,N-Me Val) 纳入中.
- 成功合成含有多达三种N-Me AAs的,模仿天然产品药物结构.
- 为 N-Me AAs 实现了更好的整合效率和翻译保真性.
结论:
- 含有多个N-Me AAs的的核糖体合成是可行的.
- 这种方法促进了非自然库的创建,用于识别新药候选药物.
- 通过这些库的体外选择,有可能发现用于治疗标的高亲缘关系联体.
相关概念视频
02:53Ribosomal RNA Synthesis
Ribosome synthesis is a highly complex and coordinated process involving more than 200 assembly factors. The synthesis and processing of ribosomal components occurs not only in the nucleolus but also in the nucleoplasm and the cytoplasm of eukaryotic cells.
Ribosome biogenesis begins with the synthesis of 5S and 45S pre-rRNAs by distinct RNA polymerases. The primary transcripts are extensively processed and modified before they are bound and folded by ribosomal proteins and assembly factors,...
Ribosome biogenesis begins with the synthesis of 5S and 45S pre-rRNAs by distinct RNA polymerases. The primary transcripts are extensively processed and modified before they are bound and folded by ribosomal proteins and assembly factors,...
02:53Ribosomal RNA Synthesis
Ribosome synthesis is a highly complex and coordinated process involving more than 200 assembly factors. The synthesis and processing of ribosomal components occurs not only in the nucleolus but also in the nucleoplasm and the cytoplasm of eukaryotic cells.
Ribosome biogenesis begins with the synthesis of 5S and 45S pre-rRNAs by distinct RNA polymerases. The primary transcripts are extensively processed and modified before they are bound and folded by ribosomal proteins and assembly factors,...
Ribosome biogenesis begins with the synthesis of 5S and 45S pre-rRNAs by distinct RNA polymerases. The primary transcripts are extensively processed and modified before they are bound and folded by ribosomal proteins and assembly factors,...
01:27Ribosomes
Ribosomes translate genetic information encoded by messenger RNA (mRNA) into proteins. Both prokaryotic and eukaryotic cells have ribosomes. Cells that synthesize large quantities of protein—such as secretory cells in the human pancreas—can contain millions of ribosomes.
Ribosome Structure and Assembly
Ribosomes are composed of ribosomal RNA (rRNA) and proteins. In eukaryotes, rRNA is transcribed from genes in the nucleolus—a part of the nucleus that specializes in ribosome production. Within...
Ribosome Structure and Assembly
Ribosomes are composed of ribosomal RNA (rRNA) and proteins. In eukaryotes, rRNA is transcribed from genes in the nucleolus—a part of the nucleus that specializes in ribosome production. Within...
01:27Ribosomes
Ribosomes translate genetic information encoded by messenger RNA (mRNA) into proteins. Both prokaryotic and eukaryotic cells have ribosomes. Cells that synthesize large quantities of protein—such as secretory cells in the human pancreas—can contain millions of ribosomes.Ribosome Structure and AssemblyRibosomes are composed of ribosomal RNA (rRNA) and proteins. In eukaryotes, rRNA is transcribed from genes in the nucleolus—a part of the nucleus that specializes in ribosome production. Within the...
01:27Ribosomes
Ribosomes translate genetic information encoded by messenger RNA (mRNA) into proteins. Both prokaryotic and eukaryotic cells have ribosomes. Cells that synthesize large quantities of protein—such as secretory cells in the human pancreas—can contain millions of ribosomes.Ribosome Structure and AssemblyRibosomes are composed of ribosomal RNA (rRNA) and proteins. In eukaryotes, rRNA is transcribed from genes in the nucleolus—a part of the nucleus that specializes in ribosome production. Within the...
01:27Ribosomes
Ribosomes translate genetic information encoded by messenger RNA (mRNA) into proteins. Both prokaryotic and eukaryotic cells have ribosomes. Cells that synthesize large quantities of protein—such as secretory cells in the human pancreas—can contain millions of ribosomes.
Ribosome Structure and Assembly
Ribosomes are composed of ribosomal RNA (rRNA) and proteins. In eukaryotes, rRNA is transcribed from genes in the nucleolus—a part of the nucleus that specializes in ribosome production. Within...
Ribosome Structure and Assembly
Ribosomes are composed of ribosomal RNA (rRNA) and proteins. In eukaryotes, rRNA is transcribed from genes in the nucleolus—a part of the nucleus that specializes in ribosome production. Within...