These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
Preprints are manuscripts made publicly available before they have been submitted for formal peer review and publication. They might contain new research findings or data. Preprints can be a draft or final version of an author's research but must not have been accepted for publication at the time of submission.
submitted on 06.02.2019 and posted on 07.02.2019by 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.