Scheuermann Jörg, Dumelin Christoph E, Melkko Samu, Neri Dario
Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zürich, Wolfgang-Pauli-Strasse 10, CH-8093 Zurich, Switzerland.
J Biotechnol. 2006 Dec 1;126(4):568-81. doi: 10.1016/j.jbiotec.2006.05.018. Epub 2006 Jun 9.
The discovery and development of novel drugs for the multitude of targets originating from functional genomic research is a challenging task. While antibodies can nowadays be raised against virtually any given target using phage-display methodologies, a similar "selection/amplification" approach for the facile discovery of low-molecular weight compounds capable of specific binding to protein targets of choice has so far been lacking. The development of DNA-encoded chemical libraries, combined with suitable selection and high-throughput sequencing strategies, holds promises to fill this gap. Here, we review the latest developments in the field of DNA-encoded chemical libraries, commenting on the challenges and opportunities for the different experimental strategies in this rapidly evolving research area, which may gain importance for the future drug discovery process.
为源自功能基因组学研究的众多靶点开发新型药物是一项具有挑战性的任务。如今,利用噬菌体展示技术几乎可以针对任何给定靶点制备抗体,但迄今为止,尚未有一种类似的“筛选/扩增”方法来轻松发现能够特异性结合所选蛋白质靶点的低分子量化合物。DNA编码化学文库的发展,结合合适的筛选和高通量测序策略,有望填补这一空白。在此,我们综述了DNA编码化学文库领域的最新进展,对这一快速发展的研究领域中不同实验策略所面临的挑战和机遇进行了评论,这可能对未来的药物发现过程具有重要意义。