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Online Size-exclusion and Ion-exchange Chromatography on a SAXS Beamline
Published on: January 5, 2017
"ワン・ビーズ・ワン・コンパウンド"のペプチドミメティックと小分子組合せライブラリのための新しいペプチドベースのエンコーディングシステム
Ruiwu Liu1, Jan Marik, Kit S Lam
1Division of Hematology & Oncology, Department of Internal Medicine, UC Davis Cancer Center, University of California-Davis, 4501 X Street, Sacramento, CA 95817, USA.
Journal of the American Chemical Society
|June 27, 2002
まとめ
新しいペプチドベースのエンコーディングシステムは",one-bead one-compound" (OBOC) ライブラリの構造決定を簡素化しています. この方法は,大規模な組み合わせライブラリから強力で新しいリガンドを効率的に識別します.
科学分野:
- 薬用化学 薬用化学について
- 組み合わせ化学は,組み合わせ化学です.
- バイオテクノロジー バイオテクノロジー
背景:
- "one-bead-one-compound" (OBOC) メソッドは,何百万もの化合物の高通量スクリーニングを可能にします.
- OBOC方法によって合成された化合物,特にペプチドミメティックおよび小分子による構造の決定は,大きな課題を提示します.
研究 の 目的:
- OBOCの組み合わせライブラリのために,新しい,効率的で堅牢なペプチドベースのエンコーディングシステムを開発する.
- ペプチドミメティックおよび小分子のOBOCスクリーニングにおける構造決定の限界を克服するために.
主な方法:
- 二相溶媒戦略を使用して作成されたトポロジカルに分離された二機能ビーズを使用しました.
- 非自然なアルファ-アミノ酸を組み込んだペプチドベースのコーディングタグを開発し,試験化合物と同時に合成しました.
- 断裂なしの正数数珠の直接配列化のためにエドマン分解を使用した.
主要な成果:
- 158,400人のメンバーをコードしたペプチドミメティックライブラリを成功裏に生成し,スクリーニングしました.
- ストライプタヴィジンと結合する独特のモチーフを持つ強力なおよび新しいリガンドが特定されました.
- ペプチドベースのエンコーディングシステムの効率とシンプルさを実証しました.
結論:
- 開発されたペプチドベースのエンコーディングシステムは,OBOCの組み合わせライブラリにとって非常に効率的で堅牢です.
- この方法は,構造の決定を簡素化し,新しい生物活性化合物の発見を促進します.
- このシステムは,追加の合成ステップを排除し,望ましくない副産物を最小限に抑えます.
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