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Incorporating a guanidine-modified cytosine base into triplex-forming PNAs for the recognition of a C-G pyrimidine–purine inversion site of an RNA duplex
RNA duplex regions are often involved in tertiary interactions and protein binding and thus there is great potential in developing ligands that sequence-specifically bind to RNA duplexes. We have developed a convenient synthesis method for a modified peptide nucleic acid (PNA) monomer with a guanidi...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5100590/ https://www.ncbi.nlm.nih.gov/pubmed/27596599 http://dx.doi.org/10.1093/nar/gkw778 |
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author | Toh, Desiree-Faye Kaixin Devi, Gitali Patil, Kiran M. Qu, Qiuyu Maraswami, Manikantha Xiao, Yunyun Loh, Teck Peng Zhao, Yanli Chen, Gang |
author_facet | Toh, Desiree-Faye Kaixin Devi, Gitali Patil, Kiran M. Qu, Qiuyu Maraswami, Manikantha Xiao, Yunyun Loh, Teck Peng Zhao, Yanli Chen, Gang |
author_sort | Toh, Desiree-Faye Kaixin |
collection | PubMed |
description | RNA duplex regions are often involved in tertiary interactions and protein binding and thus there is great potential in developing ligands that sequence-specifically bind to RNA duplexes. We have developed a convenient synthesis method for a modified peptide nucleic acid (PNA) monomer with a guanidine-modified 5-methyl cytosine base. We demonstrated by gel electrophoresis, fluorescence and thermal melting experiments that short PNAs incorporating the modified residue show high binding affinity and sequence specificity in the recognition of an RNA duplex containing an internal inverted Watson-Crick C-G base pair. Remarkably, the relatively short PNAs show no appreciable binding to DNA duplexes or single-stranded RNAs. The attached guanidine group stabilizes the base triple through hydrogen bonding with the G base in a C-G pair. Selective binding towards an RNA duplex over a single-stranded RNA can be rationalized by the fact that alkylation of the amine of a 5-methyl C base blocks the Watson–Crick edge. PNAs incorporating multiple guanidine-modified cytosine residues are able to enter HeLa cells without any transfection agent. |
format | Online Article Text |
id | pubmed-5100590 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-51005902016-11-10 Incorporating a guanidine-modified cytosine base into triplex-forming PNAs for the recognition of a C-G pyrimidine–purine inversion site of an RNA duplex Toh, Desiree-Faye Kaixin Devi, Gitali Patil, Kiran M. Qu, Qiuyu Maraswami, Manikantha Xiao, Yunyun Loh, Teck Peng Zhao, Yanli Chen, Gang Nucleic Acids Res Chemical Biology and Nucleic Acid Chemistry RNA duplex regions are often involved in tertiary interactions and protein binding and thus there is great potential in developing ligands that sequence-specifically bind to RNA duplexes. We have developed a convenient synthesis method for a modified peptide nucleic acid (PNA) monomer with a guanidine-modified 5-methyl cytosine base. We demonstrated by gel electrophoresis, fluorescence and thermal melting experiments that short PNAs incorporating the modified residue show high binding affinity and sequence specificity in the recognition of an RNA duplex containing an internal inverted Watson-Crick C-G base pair. Remarkably, the relatively short PNAs show no appreciable binding to DNA duplexes or single-stranded RNAs. The attached guanidine group stabilizes the base triple through hydrogen bonding with the G base in a C-G pair. Selective binding towards an RNA duplex over a single-stranded RNA can be rationalized by the fact that alkylation of the amine of a 5-methyl C base blocks the Watson–Crick edge. PNAs incorporating multiple guanidine-modified cytosine residues are able to enter HeLa cells without any transfection agent. Oxford University Press 2016-11-02 2016-09-04 /pmc/articles/PMC5100590/ /pubmed/27596599 http://dx.doi.org/10.1093/nar/gkw778 Text en © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Chemical Biology and Nucleic Acid Chemistry Toh, Desiree-Faye Kaixin Devi, Gitali Patil, Kiran M. Qu, Qiuyu Maraswami, Manikantha Xiao, Yunyun Loh, Teck Peng Zhao, Yanli Chen, Gang Incorporating a guanidine-modified cytosine base into triplex-forming PNAs for the recognition of a C-G pyrimidine–purine inversion site of an RNA duplex |
title | Incorporating a guanidine-modified cytosine base into triplex-forming PNAs for the recognition of a C-G pyrimidine–purine inversion site of an RNA duplex |
title_full | Incorporating a guanidine-modified cytosine base into triplex-forming PNAs for the recognition of a C-G pyrimidine–purine inversion site of an RNA duplex |
title_fullStr | Incorporating a guanidine-modified cytosine base into triplex-forming PNAs for the recognition of a C-G pyrimidine–purine inversion site of an RNA duplex |
title_full_unstemmed | Incorporating a guanidine-modified cytosine base into triplex-forming PNAs for the recognition of a C-G pyrimidine–purine inversion site of an RNA duplex |
title_short | Incorporating a guanidine-modified cytosine base into triplex-forming PNAs for the recognition of a C-G pyrimidine–purine inversion site of an RNA duplex |
title_sort | incorporating a guanidine-modified cytosine base into triplex-forming pnas for the recognition of a c-g pyrimidine–purine inversion site of an rna duplex |
topic | Chemical Biology and Nucleic Acid Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5100590/ https://www.ncbi.nlm.nih.gov/pubmed/27596599 http://dx.doi.org/10.1093/nar/gkw778 |
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