Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/150414
Title: Incorporating G-C pair-recognizing Guanidinium into PNAs for sequence and structure specific recognition of dsRNAs over dsDNAs and ssRNAs
Authors: Krishna, Manchugondanahalli S.
Wang, Zhenzhang
Zheng, Liangzhen
Bowry, Jogesh
Ong, Alan Ann Lerk
Mu, Yuguang
Prabakaran, Mookkan
Chen, Gang
Keywords: Science::Biological sciences
Issue Date: 2019
Source: Krishna, M. S., Wang, Z., Zheng, L., Bowry, J., Ong, A. A. L., Mu, Y., Prabakaran, M. & Chen, G. (2019). Incorporating G-C pair-recognizing Guanidinium into PNAs for sequence and structure specific recognition of dsRNAs over dsDNAs and ssRNAs. Biochemistry, 58(36), 3777-3788. https://dx.doi.org/10.1021/acs.biochem.9b00608
Project: RG152/17
MOE2015-T2-1-028
RG146/17
Journal: Biochemistry
Abstract: Recognition of RNAs under physiological conditions is important for the development of chemical probes and therapeutic ligands. Nucleobase-modified dsRNA-binding PNAs (dbPNAs) are promising for the recognition of dsRNAs in a sequence and structure specific manner under near-physiological conditions. Guanidinium is often present in proteins and small molecules for the recognition of G bases in nucleic acids, in cell-penetrating carriers, and in bioactive drug molecules, which might be due to the fact that guanidinium is amphiphilic and has unique hydrogen bonding and stacking properties. We hypothesized that a simple guanidinium moiety can be directly incorporated into PNAs to facilitate enhanced molecular recognition of G-C pairs in dsRNAs and improved bioactivity. We grafted a guanidinium moiety directly into a PNA monomer (designated as R) using a two-carbon linker as guided by computational modeling studies. The synthetic scheme of the PNA R monomer is relatively simple compared to that of the previously reported L monomer. We incorporated the R residue into various dbPNAs for binding studies. dbPNAs incorporated with R residues are excellent in sequence specifically recognizing G-C pairs in dsRNAs over dsDNA and ssRNAs. We demonstrated that the R residue is compatible with unmodified T and C and previously developed modified L and Q residues in dbPNAs for targeting model dsRNAs, the influenza A viral panhandle duplex structure, and the HIV-1 frameshift site RNA hairpin. Furthermore, R residues enhance the cellular uptake of PNAs.
URI: https://hdl.handle.net/10356/150414
ISSN: 0006-2960
DOI: 10.1021/acs.biochem.9b00608
Rights: This document is the Accepted Manuscript version of a Published Work that appeared in final form in Biochemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.biochem.9b00608
Fulltext Permission: open
Fulltext Availability: With Fulltext
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