SAMマチュラーゼによる多種多様なチオエーテルマクロサイクリングペプチド
Karsten A S Eastman1,2, Andrew G Roberts1, Vahe Bandarian1,2
1Department of Chemistry, The University of Utah, Salt Lake City, UT 84112.
まとめ
PapB酵素は,非自然なアミノ酸を含むペプチドで安定したチオエーテルマクロサイクルを生成する. これは,治療薬と化学生物学のアプリケーションのために制限されたペプチドを設計するためのオプションを拡張します.
科学分野:
- 生物化学
- 化学生物学
- バイオテクノロジー
背景:
- ディスルファイド結合はペプチドを安定させるが,生理学的条件下では不安定であり,バイオテクノロジーの応用を制限する.
- PapBはS-アデノシル-L-メチオニンの酵素で,ペプチドの成熟時に通常チオエーテル結合を形成する.
- リボソームで生成されたペプチドと翻訳後のペプチドは安定化戦略を必要とします.
研究 の 目的:
- 既知の機能を超えた PapB の基板範囲と酵素活性を調べる.
- 様々なアミノ酸基板を使用して新しいチオエーテルマクロサイクルを形成するパップBの可能性を調査する.
- 構造的に制約されたペプチドを作るための酵素ツールボックスを拡張します.
主な方法:
- D-アミノ酸とβ-アミノ酸を含む様々なペプチド基板を用いたPapBを用いた酵素測定.
- α-およびβ-チオエーテルマクロサイクルの形成を確認するためのペプチド産物の分析.
- ペプチド基板内の非自然なアミノ酸に対するPapBの耐性の特徴.
主要な成果:
- PapBは,D-またはβ-アミノ酸で終わるペプチドのC端カルボキシラートと内部C thiolを効率的に結合し,α-またはβ-チオエーテルマクロサイクルを形成する.
- PapBはβ-およびN-メチルアミノ酸に対する耐性を示し,非自然なアミノ酸から完全に構成されたマクロサイクルの合成を可能にします.
- PapBは,C端のマクロサイクリングのシーケンスアグノスティックチオエーテルリガゼとして機能する.
結論:
- PapBは,非自然なアミノ酸を含む多様なペプチド基板で安定したチオエーテルマクロサイクルを形成できる多用途酵素です.
- この発見により,PapBは形状的に制約されたペプチドを構成する貴重なツールとして確立された.
- この研究はペプチドベースの治療法と化学生物学の可能性を広げています.
関連する概念動画
01:10Radical Chain-Growth Polymerization: Overview
2.7K
Chain-growth or addition polymerization is successive addition reactions of monomers with a polymer chain. In radical chain-growth polymerization, the reaction proceeds via a free-radical intermediate. The free radical is formed from radical initiators, which spontaneously generate free radicals by homolytic fission. Organic peroxides (such as dibenzoyl peroxide, as shown in Figure 1) or azo compounds are popular radical initiators. A low concentration ratio of radical initiator to monomer is...
2.7K
01:28ATP and Macromolecule Synthesis
6.1K
Biological macromolecules are organic compounds, predominantly composed of carbon atoms. The carbon atoms are covalently bonded with hydrogen, oxygen, nitrogen, and other minor elements. There are four major biological macromolecule classes: carbohydrates, lipids, proteins, and nucleic acids.
Most macromolecules are composed of single subunits, or building blocks, called monomers. The monomers combine with each other using covalent bonds to form larger molecules known as polymers.
Conversion of...
Most macromolecules are composed of single subunits, or building blocks, called monomers. The monomers combine with each other using covalent bonds to form larger molecules known as polymers.
Conversion of...
6.1K
01:09Radical Chain-Growth Polymerization: Mechanism
2.8K
The radical chain-growth polymerization mechanism consists of three steps: initiation, propagation, and termination of polymerization. The polymerization initiates when a free radical generated from the radical initiator adds to the unsaturated bond in the monomer. The unpaired electron of the free radical and one π electron in the unsaturated bond creates a σ bond between the free radical and the monomer. As a result, the other π electron in the unsaturated bond converts this...
2.8K
01:17Radical Chain-Growth Polymerization: Chain Branching
2.0K
The skeletal structure of polymers synthesized via radical polymerization is always branched. For example, the polymerization of ethylene by radical polymerization results in a low-density grade of polyethylene with a heavily branched skeletal structure. Here, the radical site abstracts hydrogen from the growing chain, and the radical site shifts from the end (a primary carbon center) to anywhere within the growing chain (a secondary carbon center). Consequently, the part of the chain from the...
2.0K
01:11Radical Reactivity: Overview
2.2K
Radicals, the highly reactive species, gain stability by undergoing three different reactions. The first reaction involves a radical-radical coupling, in which a radical combines with another radical, forming a spin‐paired molecule. The second reaction is between a radical and a spin‐paired molecule, generating a new radical and a new spin‐paired molecule. The third reaction is radical decomposition in a unimolecular reaction, forming a new radical and a spin‐paired...
2.2K
01:33Radical Reactivity: Intramolecular vs Intermolecular
1.8K
Radical reactions can occur either intermolecularly or intramolecularly. In an intermolecular radical reaction, a nucleophilic radical adds to an electrophilic alkene or vice versa. In such reactions, the radical and generally the alkene, which is also called the radical trap, are two different molecules. Additionally, for such intermolecular reactions to occur, the radical trap must be active, present in an excess concentration, and the radical starting material must have a weak...
1.8K