School of Pharmacy, University of Connecticut, 69 N. Eagleville Road, Storrs, CT, 06269, USA.
Department of Chemistry, Institute for Biomolecular Design and Discovery (IBD), and CNAST, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, PA, 15213, USA.
Chembiochem. 2018 Apr 4;19(7):674-678. doi: 10.1002/cbic.201700574. Epub 2018 Feb 12.
Template-directed synthesis offers several distinct benefits over conventional laboratory creation, including unsurpassed reaction rate and selectivity. Although it is central to many biological processes, such an approach has rarely been applied to the in situ synthesis and recognition of biomedically relevant target. Towards this goal, we report the development of a three-codon nucleic-acid probe containing a C-terminal thioester group and an N-terminal cysteine that is capable of undergoing template-directed oligomerization in the presence of an RNA target and self-deactivation in its absence. The work has implications for the development of millamolecular nucleic-acid probes for targeting RNA-repeated expansions associated with myotonic dystrophy type 1 and other related neuromuscular and neurodegenerative disorders.
模板指导合成在反应速度和选择性方面优于传统的实验室合成，具有明显优势。尽管它是许多生物过程的核心，但这种方法很少应用于生物医学相关靶标的原位合成和识别。为此，我们开发了一种包含 C 端硫酯基团和 N 端半胱氨酸的三密码子核酸探针，该探针能够在 RNA 靶标的存在下进行模板指导的寡聚化，而在不存在靶标的情况下自我失活。这项工作对于开发用于靶向与肌萎缩性侧索硬化症 1 型和其他相关神经肌肉和神经退行性疾病相关的 RNA 重复扩展的毫摩尔级核酸探针具有重要意义。
