ブラディキニンにおけるコンフォーマル・レギュレッテッド・ペプチド・ボンド・クリア
Daniel R Fuller1, Christopher R Conant1, Tarick J El-Baba1
1Department of Chemistry , Indiana University , Bloomington , Indiana 47405 , United States.
Journal of the American Chemical Society
|July 21, 2018
まとめ
ブラディキニン (BK) は,温度に誘発された陽子化と異体化によって誘発されるPro2-Pro3結合でユニークな非酵素分裂を経験する. 人間の酵素に抵抗するこの内在的な経路は,ペプチド処理と抗原性についての洞察を提供します.
科学分野:
- 生物化学
- 化学物理学
- 分析化学
背景:
- ブラディキニン (BK) は,既知の生物学的機能を持つペプチドである.
- ペプチドの安定性と処理を理解することは,薬物開発と生物学的研究にとって極めて重要です.
- 固有のペプチド分裂経路は,生物学的抵抗機構の洞察を提供することができます.
研究 の 目的:
- イオン移動性および質量スペクトロメトリを使用して,異なるブラジキニン (BK) 構造の構造安定性を調査する.
- BKにおける新しい非酵素型Pro2-Pro3結合分裂のメカニズムを解明する.
- BK処理に関与する移行状態の熱力学的パラメータを決定する.
主な方法:
- 質量スペクトロメトリー (IM-MS) と結合したイオン移動スペクトロメトリー.
- 温度依存運動研究
- 陽子反応と形状の変化の分析
主要な成果:
- 高温はArg1-Pro2のトランス→シスイソメリゼーションによって調節される遅いプロトネーション反応 ([BK+2H]2+ → [BK+3H]3+) を誘導する.
- オール-シス [BK+3H]3+コンフォームは,高特異性でプロ2プロ3結合を自発的に割ります.
- この分裂は,Arg1-Pro2異体化によって調節される複数の中間物質によって発生し,生物学的にも耐性がある.
- 陽子化と結合分裂のための移行状態熱化学を決定した.
結論:
- Pro2-Pro3結合におけるブラジキニンの新しい非酵素分裂経路が特定された.
- この経路はArg1-Pro2のトランス→シスイソメリゼーションとプロトネーションによって制御される.
- この内在的処理経路に対する生物学的抵抗は,ペプチド抗原性に影響する.
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