タンパク質におけるアミドカルボニル-カルボニル相互作用の性質
Amit Choudhary1, Deepa Gandla, Grant R Krow
1Graduate Program in Biophysics, University of Wisconsin, Madison, Wisconsin 53706, USA.
Journal of the American Chemical Society
|May 28, 2009
まとめ
タンパク質の隣接するカルボニル基間の相互作用は,主に電子離位によるもので,電荷相互作用によるものではない. この発見は,生物分子構造と相互作用に関する私たちの理解に影響を与えます.
科学分野:
- バイオケミストリー バイオケミストリー
- 構造生物学 構造生物学とは
- コンピューティング・ケミストリー
背景:
- 非共性相互作用は,バイオ分子構造,機能,動力学にとって根本的なものです.
- タンパク質の二次構造における隣接するカルボニル群は,安定性とリガンド結合に不可欠な密接な相互作用を示す.
研究 の 目的:
- ペプチド結合における隣接するカルボニル基間の密接な相互作用の主要な起源を解明する.
- この相互作用の原因として,電荷対電荷,二極対二極,およびn-->pi*電子離位を区別する.
主な方法:
- イソステル化学代用剤を用いたペプチドモデルシステムを活用した.
- 分析のための核磁気共振 (NMR) スペクトロスコーピーを使用しました.
- X線微分分析を実施しました.
- Ab initio量子化学計算を行いました.
主要な成果:
- 隣接するカルボニル基間の密接な相互作用は,主にn->pi*電子移位から生じることを示した.
- この電子移位は,隣接するカルボニルグループの抗結合軌道と相互作用する1つのペプチド結合の酸素上の単一のペアを含む.
- 主要な要因として,電荷対電荷または二極二極相互作用を排除した.
結論:
- n->pi*電子移位は,タンパク質の隣接するカルボニル同士の密接な接触の主な要因である.
- この理解は,有機化学,生化学,医薬品化学に重大な影響を及ぼします.
- タンパク質の構成的安定性とタンパク質-リガンドの相互作用に対するエネルギーの貢献に関する洞察を提供します.
関連する概念動画
01:28Structures of Carboxylic Acid Derivatives
Structure of Carboxylic Acid Derivatives
Carboxylic acid derivatives contain an acyl group attached to a heteroatom such as chlorine, oxygen, or nitrogen. The carbonyl carbon and oxygen are both sp2-hybridized with an unhybridized p orbital.
The three sp2 orbitals of the carbonyl carbon form three σ bonds, one each with the carbonyl oxygen, the α carbon, and the heteroatom, whereas the other two sp2 orbitals of the carbonyl oxygen are occupied by the lone pairs. Further, the unhybridized p...
Carboxylic acid derivatives contain an acyl group attached to a heteroatom such as chlorine, oxygen, or nitrogen. The carbonyl carbon and oxygen are both sp2-hybridized with an unhybridized p orbital.
The three sp2 orbitals of the carbonyl carbon form three σ bonds, one each with the carbonyl oxygen, the α carbon, and the heteroatom, whereas the other two sp2 orbitals of the carbonyl oxygen are occupied by the lone pairs. Further, the unhybridized p...
01:28Amides to Carboxylic Acids: Hydrolysis
Amides can undergo either acid-catalyzed hydrolysis or base-promoted hydrolysis through a typical nucleophilic acyl substitution. Each hydrolysis requires severe conditions.
Acid-catalyzed hydrolysis:
Hydrolysis of amides under acidic conditions yields carboxylic acids. Since the reaction occurs slowly, hydrolysis requires the conditions of heat.
The mechanism begins with the protonation of the carbonyl oxygen by the acid catalyst. The protonation makes the amide carbonyl carbon more...
Acid-catalyzed hydrolysis:
Hydrolysis of amides under acidic conditions yields carboxylic acids. Since the reaction occurs slowly, hydrolysis requires the conditions of heat.
The mechanism begins with the protonation of the carbonyl oxygen by the acid catalyst. The protonation makes the amide carbonyl carbon more...
01:19Amines to Amides: Acylation of Amines
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 amide...
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary amide...
01:29Preparation of Amides
Amides are synthesized by treating carboxylic acids with amines in the presence of dehydrating agents like dicyclohexylcarbodiimide (DCC).
The DCC-promoted synthesis of amides begins with the protonation of DCC by carboxylic acid. The protonation makes it a better acceptor. Next, the addition of carboxylate to the protonated carbodiimide gives a reactive acylating agent.
Subsequently, the amine acts as a nucleophile that attacks the acylating agent to form a tetrahedral intermediate. In the...
The DCC-promoted synthesis of amides begins with the protonation of DCC by carboxylic acid. The protonation makes it a better acceptor. Next, the addition of carboxylate to the protonated carbodiimide gives a reactive acylating agent.
Subsequently, the amine acts as a nucleophile that attacks the acylating agent to form a tetrahedral intermediate. In the...
01:16Aldehydes and Ketones with Amines: Imine and Enamine Formation Overview
Primary amines react with carbonyl compounds—aldehydes and ketones—to generate imines. Imines consist of a C=N double bond and are named Schiff bases after its discoverer—the German chemist Hugo Schiff. On the other hand, secondary amines react with carbonyl compounds to give enamines. In enamines, the presence of a C=C double bond adjacent to the nitrogen atom leads to the delocalization of the lone pair.
01:15Carboxylic Acid Derivatives: Overview
Carboxylic acid derivatives are formed by replacing the hydroxyl group of carboxylic acids with a different functional group. The most common carboxylic acid derivatives are: