用于药物发现的寡核苷酸组合文库的合理筛选。
Rational screening of oligonucleotide combinatorial libraries for drug discovery.
作者信息
Ecker D J, Vickers T A, Hanecak R, Driver V, Anderson K
机构信息
ISIS Pharmaceuticals, Carlsbad, CA 92008.
出版信息
Nucleic Acids Res. 1993 Apr 25;21(8):1853-6. doi: 10.1093/nar/21.8.1853.
Abstract
Combinatorial strategies offer the potential to generate and screen extremely large numbers of compounds and to identify individual molecules with a desired binding specificity or pharmacological activity. We describe a combinatorial strategy for oligonucleotides in which the library is generated and screened without using enzymes. Freedom from enzymes enables the use of oligonucleotide analogues. This dramatically extends the scope of both the compounds and the targets that may be screened. We demonstrate the utility of the method by screening 2'-O-Methyl and phosphorothioate oligonucleotide analogue libraries. Compounds have been identified that bind to the activated H-ras mRNA and that have potent antiviral activity against the human herpes simplex virus.
摘要
组合策略提供了生成和筛选大量化合物以及鉴定具有所需结合特异性或药理活性的单个分子的潜力。我们描述了一种用于寡核苷酸的组合策略，其中文库的生成和筛选不使用酶。无需酶使得能够使用寡核苷酸类似物。这极大地扩展了可筛选的化合物和靶标的范围。我们通过筛选2'-O-甲基和硫代磷酸酯寡核苷酸类似文库证明了该方法的实用性。已鉴定出与活化的H-ras mRNA结合且对人单纯疱疹病毒具有强效抗病毒活性的化合物。
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