Bifacial Peptide Nucleic Acid as an Allosteric Switch for Aptamer and Ribozyme Function

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• 作者：Xin Xia ; Xijun Piao ; Dennis Bong
• 刊名：Journal of the American Chemical Society
• 出版年：2014
• 出版时间：May 21, 2014
• 年：2014
• 卷：136
• 期：20
• 页码：7265-7268
• 全文大小：331K
• 年卷期：v.136,no.20(May 21, 2014)
• ISSN：1520-5126

文摘

We demonstrate herein that bifacial peptide nucleic acid (bPNA) hybrid triplexes functionally substitute for duplex DNA or RNA. Structure鈥揻unction loss in three non-coding nucleic acids was inflicted by replacement of a duplex stem with unstructured oligo-T/U strands, which are bPNA binding sites. Functional rescue was observed on refolding of the oligo-T/U strands into bPNA triplex hybrid stems. Bifacial PNA binding was thus used to allosterically switch-on protein and small-molecule binding in DNA and RNA aptamers, as well as catalytic bond scission in a ribozyme. Duplex stems that support the catalytic site of a minimal type I hammerhead ribozyme were replaced with oligo-U loops, severely crippling or ablating the native RNA splicing function. Refolding of the U-loops into bPNA triplex stems completely restored splicing function in the hybrid system. These studies indicate that bPNA may have general utility as an allosteric trigger for a wide range of functions in non-coding nucleic acids.