Modified oligonucleotides are versatile in their uses in academia to perturb biological systems or in industry to design new biotechnology and therapeutics. To function properly, some oligonucleotides require a protein-binding event. The goal of this project is to develop a method for screening RNA modifications that enhance protein-RNA binding. The sample system we will be using is Adenosine Deaminase Acting on RNA 2 (ADAR2) because it binds double stranded RNA (dsRNA). Thiol modified RNA is made via a purine C2 tethered ethanethiol phosphoramidite. MALDI conditions have been established to monitor tethering reactions in RNA-protein complexes. Lead modifications will be determined by mass spectroscopy and subjected to binding studies.  Ultimately, the uses for this type of modification could be improvements of siRNA, antisense oligonucleotides that employ RNAse H, or to improve guide strands for directed RNA editing.

Enhanced oligonucleotide binding by RNA tethering in deaminase acting on RNA 2 (ADAR2)

251st National Meeting (2016)

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