ガス相単水ニコチンの構造:アセチルコリン結合タンパク質におけるニコチンの原生構造への影響
Garrett D Santis1, Naoya Takeda2,3, Keisuke Hirata2,4,5
1Department of Chemistry, University of Washington, Seattle, Washington 98195, United States.
Journal of the American Chemical Society
|August 31, 2022
まとめ
単水ニコチン (NIC) とノルニコチン (NOR) の構造と赤外線スペクトルを研究した. ガス相の研究で水があることが判明
科学分野:
- 物理化学
- スペクトロスコーピー
- コンピュータ化学
背景:
- ニコチンの生物学的活性には,そのプロトネーション部位 (ピロリジンまたはピリジン) が影響する.
- これまでの研究では プロトネーション部位を間接的にしか推測できなかった.
- 生物系におけるプロトネーションの調節における水の役割は不明である.
研究 の 目的:
- ガス相単水ニコチン (NIC) とノルニコチン (NOR) のプロトネーション部位を決定する.
- これらの複合体の構造とスペクトルの性質を調査する.
- 生物学的活動とタンパク質内環境との関連付け
主な方法:
- 温度制御のダブルイオントラップを使用したガス相赤外線スペクトロスコーピー.
- イオン製剤の衝突剥離法
- スペクトルと構造分析のための高レベルの理論的計算.
主要な成果:
- ピリジンとピロリジンのモノヒドレットニコチンカチオン (NICH+) のプロトネーション比は,240 Kで8:2と決定された.
- この比率は,非水性NICH+ (3:2) と水溶液 (主にピロリジン) と著しく異なる.
- ノルニコチンについては,ピリジン陽子型 (Pyri-NORH+) のみ観察された.
結論:
- ガス相における単一の水分子は,ニコチンのプロトネーションの好みを大きく変化させます.
- モノヒドラットされたNICH+の観測されたプロトネーション比は,アセチルコレリン結合タンパク質 (AChBP) の環境を模倣する.
- ノルニコチンのピリジンプロトネーションは,生物学的活性低下と関連している可能性があります.
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