Small-Molecule Screening Made Simple for a Difficult Target with a Signaling Nucleic Acid Aptamer that Reports on Deaminase Activity

✍ Scribed by Nadine H. Elowe; Razvan Nutiu; Abdellah Allali-Hassani; Jonathan D. Cechetto; Donald W. Hughes; Yingfu Li; Eric D. Brown

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 401 KB
• Volume: 45
• Category: Article
• ISSN: 0044-8249
• DOI: 10.1002/anie.200601695

✦ Synopsis

Conventional approaches to small-molecule screening are currently being challenged by the availability of vast amounts of genomic sequence information and a plethora of potential targets. This challenge has precipitated a need for new screening paradigms that emphasize simplicity, capacity, and parallelization. Herein we report the application of signaling DNA-aptamer technology for the development and execution of a high-throughput screen for an otherwise problematic target, adenosine deaminase (ADA). The approach employed a signaling DNA aptamer that reports on adenosine concentration over the course of the enzymatic reaction. The assay was extremely robust in a screen of more than 44 000 molecules and revealed a new competitive inhibitor of the deaminase. Nucleic acid aptamers have proven worthy as a routinely selectable species for a wide variety of small molecules and so this proof-of-principle work has broad

[*] N.