RNA is most commonly known as a mediator between the genetic code of DNA and polypeptides. However, RNA also facilitates a variety of catalytic and regulatory functions within the cell, making it a desirable target for molecular recognition. This holds true for regions of double-stranded RNA (dsRNA) whose presence is more extensive than originally thought. One tool known for the molecular recognition of dsRNA is peptide nucleic acids (PNA) which incorporate synthetic nucleobases into a flexible, neutrally charged backbone capable of selective binding with Watson-Crick base pairs in dsRNA. Current approaches that involve nucleobases attached to PNA focus on recognition of a single base in the Watson-Crick base pair through Hoogsteen hydrogen bonding. However, the ability to recognize both Watson-Crick bases simultaneously across the entire Hoogsteen face should afford stronger interactions and higher affinity for dsRNA. We are targeting the G-C base pair by linking synthetic nucleobases that, independently, have high binding affinity with each base of the Watson-Crick base pair in nucleobase 3. Analogues 1 and 2 are derived from known PNA nucleobases 2-aminopyridine (M) and 2-pyrimidinone (P), which interact favorably with G and C in dsRNA, respectively. Ultimately, the binding affinity of 3 with the G-C base pair will be evaluated through NMR titrations. The research represented here is a collaborative project between Elizabethtown College’s senior capstone course and the Rozners group at Binghamton University.

Design of a bifunctional nucleobase for molecular recognition of G-C base pairs in double-stranded RNA

255th National Meeting (2018)

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