DNAを不活性四極アンモニア基板に逆結合してDNAエンコードされたライブラリ合成における反応性の拡大
Dillon T Flood1, Shota Asai1, Xuejing Zhang1,2
1Department of Chemistry , Scripps Research , 10550 North Torrey Pines Road , La Jolla , California 92037 , United States.
Journal of the American Chemical Society
|May 29, 2019
まとめ
DNAエンコードライブラリ (DEL) は,大量の化合物のスクリーニングを可能にします. 新しいリバーシブル・アドソープション・トゥ・ソリッド・サポート (RASS) 方法は,DEL化学を拡張し,新しい反応とより多様な薬剤のようなライブラリを可能にします.
科学分野:
- 薬剤化学
- 合成化学
- バイオテクノロジー
背景:
- DNAエンコードライブラリ (DEL) は 鉛の識別に強力で 何十億もの化合物をスクリーニングします
- DNAタグの水性性質は,DELで適用可能な化学成分を制限しています.
- 固体への可逆吸附 (RASS) は,非共性吸附によるバイオ分子改変を可能にします.
研究 の 目的:
- 化学的制約を克服するためにRASSをDELに適応させる.
- DELのほぼ無水状態での有機溶剤での反応を可能にします.
- 薬のようなライブラリを 開発すること
主な方法:
- DNAエンコードライブラリ合成のためのRASS戦略の適応.
- リバーシブルアドソープションを用いた有機溶剤の合成改変を行う.
- 新しく開発された化学を統合したDELリハーサルによるデモ.
主要な成果:
- 幅広い基板範囲を持つC ((sp2) -C ((sp3) デカルボキシル化クロスカップリングを有効にします.
- 電気化学アミネーションを初めて開発した.
- 還元性アミネーション条件を改善し,DELリハーサルで有用性を証明しました.
結論:
- RASSは,以前はアクセスできない新しいDELの反応性にアクセスできます.
- このアプローチは,DELの構築のための化学空間を拡大します.
- RASSは より多様で薬物に似た 図書館の作成を容易にするのです
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