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Synthetic bPNAs as Allosteric Triggers of Hammerhead Ribozyme Catalysis

preprint
submitted on 06.02.2019 and posted on 07.02.2019 by Dennis Bong, Yufeng Liang, Jie Mao
The biochemistry and structural biology of the hammerhead ribozyme (HHR) has been well-elucidated. The secondary and tertiary structural elements that enable sugar-phosphate bond scission to be be catalyzed by this RNA are clearly understood. We have taken advantage of this knowledge base to test the extent to which synthetic molecules, may be used to trigger structure in secondary structure and tertiary interactions and thereby control HHR catalysis. These molecules belong to a family of molecules we call generally call “bPNAs” based on our work on bifacial peptide nucleic acid (bPNA). This family of molecules display the “bifacial” heterocycle melamine, which acts as a base-triple upon capturing two equivalents of thymine or uracil. Loosely structured internal oligouridylate bulges of 4-20 nucleotides can be restructured as triplex hybrid stems upon binding bPNAs. As such, a duplex stem element can be replaced with a bPNA triplex hybrid stem; similarly, a tertiary loop-stem interaction can be replaced with a loop-bPNA-stem complex. In this chapter, we discuss how bPNAs are prepared and applied to study structure-function turn-on in the hammerhead ribozyme system.

Funding

GM111995-01A1

GRT00044810

DMR 1802432

History

Email Address of Submitting Author

bong.6@osu.edu

Institution

The Ohio State University

Country

USA

ORCID For Submitting Author

0000-0003-3778-9183

Declaration of Conflict of Interest

none

Version Notes

version one

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