The importance of non-coding RNAs in cell biology makes them attractive targets for molecular recognition. However, designing of small molecules that selectively recognize RNA has been a challenging and involved process because RNA helix presents little opportunity for shape-selective recognition. We discovered (1) that nucleobase-modified peptide nucleic acids (PNA), as short as six nucleobases, bind with low nanomolar affinity and high sequence selectively to double-stranded RNA via triple helix formation under physiological conditions.Interestingly, little to no binding is observed to dsDNA of the same sequence, which suggests that the modified PNAs have unique selectivity for dsRNA. We also demonstrated that this binding could be used for highly specific recognition of biologically important double stranded RNA, such as ribosomal RNA and microRNAs. PNAs carrying M  and Lys modifications were efficiently taken up by HEK-293 cells, while the unmodified PNA showed little uptake (2). This presentation will discuss our most recent results on sequence selective recognition of biologically relevant double-stranded RNAs using chemically modified PNA analogues under physiological conditions.1. Zengeya, T.; Gupta, P.; Rozners, E.  Triple Helical Recognition of RNA Using 2-Aminopyridine-Modified PNA at Physiologically Relevant Conditions. Angew. Chem., Int. Ed. 2012  , 51, 12593-12596 (VIP).2. Muse, O.; Zengeya, T.; Mwaura, J.; Hnedzko, D.; McGee, D. W.; Grewer, C. T.; Rozners, E. ACS Chem. Biol. 2013  , 8, 1683�1686.

Sequence selective recognition of double-stranded RNA using nucleobase-modified peptide nucleic acids

247th National Meeting (2014)

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