In Vitro ディスプレイと互換性のある脊椎周期ペプチドのリボソーム合成
Ryo Takatsuji1, Koki Shinbara1, Takayuki Katoh1
1Department of Chemistry, Graduate School of Science , The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku , Tokyo 113-0033 , Japan.
Journal of the American Chemical Society
|January 17, 2019
まとめ
この研究は,現在の in vitro 表示技術の限界を克服し,バックボーンサイクルペプチドを表示するための新しい方法を導入しています. この突破はペプチド"フェノタイプ"と"ゲノタイプ"を ユニークなクロスリンク戦略で結びつけることで 治療開発を可能にします
科学分野:
- 生物化学
- 分子生物学
- 薬剤化学
背景:
- 脊髄循環ペプチドは 薬の開発に有望です
- 現行のin vitro表示技術は,フェノタイプとゲノタイプを結びつけるC末端領域の喪失のために,脊椎周期性ペプチドには使用できません.
研究 の 目的:
- 脊髄循環ペプチドをインビトロ表示技術を用いて表示するための方法論を開発する.
- 脊髄循環ペプチドの 治療開発を可能に
主な方法:
- 遺伝子コードを再プログラムして 特定のサイドチェーンを持つ デザイナー・イニシアターを組み込む
- シアゾリジンで保護されたシステインと2 - クロロアセトアミド (ClAc) を含む再配置戦略を使用します.
- 突発的なチオエステル再配列と分子内原生化学結合を用いてクロスリンクする.
主要な成果:
- 脊髄循環ペプチドの表示を可能にする新しい方法が成功裏に開発されました.
- 方法論は,サイドチェーンチオエーテルリンクを通じてC端ペプチド領域の保持を保証する.
- 様々な配列とリングサイズのインビトロ表示と互換性が実証された.
結論:
- 開発された方法論は,バックボーンサイクルペプチドを表示する以前の制限を克服しています.
- このアプローチは,骨幹型サイクリックペプチドの開発のための in vitro 表示技術の使用を容易にする.
- 脊髄循環性ペプチドの 治療への新たな道を開く
関連する概念動画
02:53Ribosomal RNA Synthesis
14.8K
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,...
14.8K
02:53Ribosomal RNA Synthesis
4.4K
4.4K
01:27Ribosomes
75.6K
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...
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...
75.6K
01:27Ribosomes
10.9K
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...
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...
10.9K
02:43Peptide Bonds
82.9K
A peptide bond covalently attaches amino acids through a dehydration reaction. One amino acid's carboxyl group and another amino acid's amino group combine, releasing a water molecule. The resulting bond is the peptide bond. The products that such linkages form are peptides. As more amino acids join this growing chain, the resulting chain is a polypeptide. Each polypeptide has a free amino group at one end. This end has the N-terminal, or the amino-terminal, and the other end has a free...
82.9K
02:24Ribosome Profiling
4.2K
Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
4.2K