フォスフォノアセテートとチオフォスフォノアセテートオリゴデオキシヌクレオチドの固体相化学合成

Douglas J Dellinger¹, David M Sheehan, Nanna K Christensen

¹Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309-0215, USA.

Journal of the American Chemical Society

|January 23, 2003

まとめ

新種のフォスフォノアセテートとチオフォスフォノアセテートオリゴデオキシヌクレオチドは,固体相法を用いて合成されました. これらの改変DNAアナログは安定しており,RNase H1の活性を刺激します.

科学分野:

オリゴヌクレオチド化学オリゴヌクレオチド化学
薬用化学薬用化学について

背景:

オリゴデオキシヌクレオチドは,分子生物学と治療において極めて重要です.
改変されたオリゴヌクレオチドを開発することで,安定性と生物学的活性が向上します.

研究の目的:

新種のフォスフォノアセテートとチオフォスフォノアセテートオリゴデオキシヌクレオチドを合成する.
これらの改変DNAアナログの安定性と酵素活性を評価するために.

主な方法:

新種のフォスフィノダイアミドイト単体を使用した固体相合成.
リン酸改変による自動DNA合成.
HPLCによる定量的酸化と浄化.
NMRと質量スペクトロメトリを用いた特徴付け.

主要な成果:

>97%の結合効率でフォスフォノアセテートとチオフォスフォノアセテートオリゴデオキシヌクレオチドを合成しました.
改変されたオリゴヌクレオチドは,ヘビの毒のリン酸化エステラゼに対する安定性を示した.
アナログは,RNase H1活動の刺激を示した.

結論:

開発された固体相戦略により,フォスフォノアセテートおよびチオフォスフォノアセテート改変オリゴヌクレオチドの効率的な合成が可能です.
これらの新しいアナログは,ニュクレアゼ抵抗性およびRNase H1相互作用を含む好ましい生化学的特性を有しています.

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