非自然なアミノ酸で,βシートの折り畳みとペプチドの相互作用を誘発する
James S Nowick1, Kit S Lam, Tatyana V Khasanova
1Department of Chemistry, University of California Irvine, Irvine, California 92697-2025, USA. jsnowick@uci.edu
Journal of the American Chemical Society
|May 2, 2002
まとめ
新しいアミノ酸であるOrn(i-PrCO-Haoは,ペプチドがベータシート構造を形成し,二元化することを可能にします. このユニークなアミノ酸は,ペプチドの配列を変えることなく構造を誘導し,制御されたペプチドの折り畳みと相互作用を促進するスプリントとして作用します.
科学分野:
- ペプチド化学 ペプチド化学
- バイオ分子工学とは
- オーガニック・シンセシス オーガニック・シンセシス
背景:
- ベータシートなどのペプチド二次構造は,タンパク質の機能に不可欠です.
- 予測可能な構造と自己組み立て特性を持つペプチドを設計することは,依然として課題です.
- ベータシート構造を誘導するための既存の方法は,重要な配列修正を伴う可能性があります.
研究 の 目的:
- ペプチドのベータシート状構造を誘導するための新しいアミノ酸派生物,Orn(i-PrCO-Hao) を導入する.
- 標準合成方法を使用して,Orn(i-PrCO-Hao) のペプチド配列への容易な組み込みを実証する.
- Orn(i-PrCO-Hao) を組み込むことで,ペプチドの折りたたみと二分化に及ぼす構造的影響を調査する.
主な方法:
- Orn ((i-PrCO-Hao) とそのFmocで保護された誘導体の合成.
- 自動化されたFmoc固相ペプチド合成により,新しいアミノ酸を組み込む.
- 核磁共振 (NMR) スペクトロスコーピー (横-ROESY,結合定数,化学シフト) でペプチドの構造と形状を分析する.
主要な成果:
- Fmoc-Orn(i-PrCO-Hao) -OH誘導体は成功して合成され,ペプチドに組み込まれました.
- 内部にOrn(i-PrCO-Hao) を含んだペプチド4は,CDCl3.3で二次元ベータシート状の構造を形成した.
- ペプチド5は,N末端のOrn(i-PrCO-Hao),折りたたまれたが,CD3ODで二酸化しなかった.
- Orn ((i-PrCO-Hao) は構造的なスプリントとして作用し,最小限のシーケンスの干渉でβシート形成を誘導します.
結論:
- 新型アミノ酸Orn(i-PrCO-Hao) は,ベータシート構造を効果的に誘導し,ペプチドにおける二酸化を促進します.
- このアミノ酸は,特定の二次構造と自己組み立て特性を持つペプチドを設計するための多用途のツールを提供します.
- Orn ((i-PrCO-Hao) は,ネイティブの残留物を置き換えることなくペプチドの折り畳みを制御する方法を提供し,サイドチェーン機能を維持します.
関連する概念動画
Protein Organization
Overview
Brønsted-Lowry Acids and Bases
In 1923, the Brønsted–Lowry definition of acids and bases was proposed by Johannes Brønsted and Thomas Lowry. According to this theory, a Brønsted acid is defined as a species that donates a proton in a chemical reaction and gets converted to its conjugate base. A Brønsted base is defined as a species that accepts a proton in a chemical reaction and gets converted into its conjugate acid. These transfers of protons are caused by the displacement of electrons in these reactions, which is...
Structures 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...
What are Proteins?
Proteins are polymers of amino acids linked together by peptide bonds. Proteins and polypeptides are interchangeably used to refer to long chains of amino acids. However, polypeptides have a molecular weight of fewer than 10,000 daltons, while proteins have greater molecular weight. Polypeptides with less than 20 amino acids are called oligopeptides or simply peptides. Interactions among the constituent amino acid side chains of proteins help them fold into a stable 3-dimensional structure...
Protein Organization
Proteins are polymers of amino acid residues. They are versatile and responsible for different cellular functions, including DNA replication, molecular transport, catalysis, and structural support. Proteins have a hierarchical structure comprising at least three levels of organization: primary, secondary, and tertiary structure. Some large proteins have a quaternary structure where individual protein subunits are linked together.
The primary structure of a protein is its amino acid sequence.
The primary structure of a protein is its amino acid sequence.
Hydrogen Bonds
A hydrogen bond is formed when a weakly positive hydrogen atom already bonded to one electronegative atom (for example, the oxygen in the water molecule) is attracted to another electronegative atom from another polar molecule, such as water (H2O), hydrogen fluoride (HF), or ammonia (NH3). The huge electronegativity difference between the H atom (2.1) and the atom to which it is bonded (4.0 for an F atom, 3.5 for an O atom, or 3.0 for an N atom), combined with the very small size of an H atom...


