Burgstaller Petra, Girod Anne, Blind Michael
NasaCell, Bahnhofstrasse 9-15, 82327 Tutzing, Germany.
Drug Discov Today. 2002 Dec 15;7(24):1221-8. doi: 10.1016/s1359-6446(02)02522-9.
The increasing number of potential drug target candidates has driven the development of novel technologies designed to identify functionally important targets and enhance the subsequent lead discovery process. Highly specific synthetic nucleic acid ligands--also known as aptamers--offer a new exciting route in the drug discovery process by linking target validation directly with HTS. Recently, aptamers have proven to be valuable tools for modulating the function of endogenous cellular proteins in their natural environment. A set of technologies has been developed to use these sophisticated ligands for the validation of potential drug targets in disease models. Moreover, aptamers that are specific antagonists of protein function can act as substitute interaction partners in HTS assays to facilitate the identification of small-molecule lead compounds.
潜在药物靶点候选物数量的不断增加推动了旨在识别功能重要靶点并加强后续先导化合物发现过程的新技术的发展。高度特异性的合成核酸配体——也称为适配体——通过将靶点验证与高通量筛选直接联系起来，为药物发现过程提供了一条令人兴奋的新途径。最近，适配体已被证明是在天然环境中调节内源性细胞蛋白功能的有价值工具。已经开发出一套技术，利用这些精密配体在疾病模型中验证潜在药物靶点。此外，作为蛋白质功能特异性拮抗剂的适配体可在高通量筛选分析中充当替代相互作用伙伴，以促进小分子先导化合物的识别。
