薬剤候補としてのマクロサイクルペプチド:最近の進歩と残る課題
Alexander A Vinogradov1, Yizhen Yin1, Hiroaki Suga1
1Department of Chemistry, Graduate School of Science , The University of Tokyo , 7-3-1 Hongo , Bunkyo-ku, Tokyo 113-0033 , Japan.
Journal of the American Chemical Society
|February 16, 2019
まとめ
ペプチド治療は有望ですが,安定性や発射に問題があります. このレビューでは,治療の成功のためにペプチド薬の特性を高めるために,マクロサイクライゼーションや非ネイティブアミノ酸のような戦略を探索しています.
科学分野:
- 薬剤化学
- 薬物の発見
- バイオテクノロジー
背景:
- ペプチドは,合成アクセシビリティと特定の結合により,魅力的な治療薬です.
- ペプチド薬の臨床的成功を制限する.
- タンパク質の表面を標的とするのはペプチド治療の重要な利点です.
研究 の 目的:
- ペプチド薬の性能を改善するための戦略をレビューする.
- ペプチド薬理の改善における進歩と課題を分析する.
- 最適なペプチド薬候補の相互矛盾する考慮のバランスを検討する.
主な方法:
- ペプチド薬の開発のためのマクロサイクライゼーション技術のレビュー.
- ペプチド設計における非タンパク質アミノ酸の組み込みの分析
- ペプチド薬の特性改善のための結合戦略の検討.
主要な成果:
- マクロサイクリング,非原生アミノ酸,結合はペプチドの代謝安定性と細胞の透過性を高めます.
- これらの改変は,新たに発見された生物活性ペプチドの限界を克服することができます.
- 最近の進歩は,個々の薬理学的特性を改善する可能性を示しています.
結論:
- ペプチド候補薬の最適化には,複数の薬理学的性質のバランスをとる必要があります.
- ペプチド治療の進歩には 矛盾する考察を結びつけることが重要です
- 戦略的改変は,薬物開発の固有のペプチドの制限を克服するための経路を提供します.
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