ペプチドとタンパク質におけるアルギニンの化学カルボニル化

Lyndsey Prosser¹, Benjamin Emenike¹, Pinki Sihag¹

¹Department of Chemistry, Emory University, Atlanta, Georgia 30322, United States.

Journal of the American Chemical Society

|March 15, 2025

まとめ

研究者は,タンパク質のアルギニン残留物を改変する新しい化学的方法を開発し,アルギニン炭化化後の改変 (PTM) と酸化ストレスにおけるその役割の研究を可能にしました.

科学分野:

生物化学
化学生物学
プロテオミクス

背景:

アルギニンの低反応性により,アルギニンの炭化化後の翻訳変化 (PTM) は十分に研究されていない領域である.
既存の方法は,PTMを研究するためにアルギニン残基を効率的に修正するために苦労しています.

研究の目的:

アルギニン炭化 PTM の化学選択的組み込みのための新しい化学的戦略を開発する.
アルギニンの残留物への自然および非自然PTMの標的化された導入を可能にします.
化学プロテオミクスのプロファイリングを容易にし,アルギニンPTMが細胞プロセスに与える影響を理解する.

主な方法:

アルギニンの金属触媒酸化 (MCO) にインスパイアされた化学的方法論を開発した.
ペプチドとタンパク質のアルギニン残基から生成されたグルタミン-5-セミアルデヒド.
様々なPTMを選択的に導入する戦略を適用した.

主要な成果:

アルギニンからグルタマート-5-セミアルデヒドを生成し,固有の低反応性を克服した.
自然と非自然の両方の PTM の選択的組み込みが示されました.
PTM分析の強固で迅速な技術を確立しました.

結論:

新しい化学的アプローチは,アルギニン炭化PTMを研究するための多用途のプラットフォームを提供します.
このPTMに敏感なアルギニンの部位の化学タンパク質分析を可能にします.
タンパク質と細胞機能に対する酸化ストレスの影響を理解する.

さらに関連する動画

10:01

In vitro Methylation Assay to Study Protein Arginine Methylation

Published on: October 5, 2014

15.2K

07:31

Nitropeptide Profiling and Identification Illustrated by Angiotensin II

Published on: June 16, 2019

5.6K

関連する概念動画

01:19

Amines to Amides: Acylation of Amines

2.3K

Various carboxylic acid derivatives (such as acid chlorides, esters, and anhydrides) can be used for the acylation of amines to yield amides. The reaction requires two equivalents of amines. The first amine molecule functions as a nucleophile and attacks the carbonyl carbon to produce a tetrahedral intermediate. This is followed by the loss of the leaving group and restoration of the C=O bond.
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary...

2.3K

02:43

Peptide Bonds

72.0K

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...

72.0K

01:13

Preparation of Carboxylic Acids: Carboxylation of Grignard Reagents

4.3K

Carboxylic acids can be prepared by the carboxylation of Grignard reagents (RMgX). This method is convenient for converting alkyl (primary, secondary or tertiary), vinyl, benzyl, and aryl halides to carboxylic acids with one additional carbon than the starting RMgX.

4.3K

03:42

Amino acids

87.6K

Amino acids are the monomers that comprise proteins. Each amino acid has the same fundamental structure, which consists of a central carbon atom, or the alpha (α) carbon, bonded to an amino group (NH2), a carboxyl group (COOH), and to a hydrogen atom. Every amino acid also has another atom or group of atoms bonded to the central atom known as the R group. There are 20 common amino acids present in proteins, each with a different R group. Variation in the amino acid sequence is responsible...

87.6K

01:24

Phase II Reactions: Acetylation Reactions

152

Acetylation, a phase II biotransformation reaction, introduces an acetyl group to drugs or their metabolites. Acetyltransferase enzymes facilitate this reaction, which resembles α-amino acid conjugation due to the addition of a functional group to the drug molecule.
The substrates for acetylation are typically drugs or their metabolites with an amino, sulfonamide, or hydrazine functional group. Acetylation can occur at several points in the drug molecule, including primary, secondary, and...

152

02:04

Covalently Linked Protein Regulators

6.7K

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....