General Recognition of U-G, U-A, and C-G Pairs by Double-Stranded RNA-Binding PNAs Incorporated with an Artificial Nucleobase
| Autor: | Jia Sheng, Katsutomo Okamura, Yunpeng Lu, Alan Ann Lerk Ong, Desiree-Faye Kaixin Toh, Gang Chen, Zhenyu Meng, Kiran M. Patil, Gitali Devi, Phensinee Haruehanroengra, Zhen Yuan, Manchugondanahalli S Krishna, Kelin Xia |
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| Přispěvatelé: | Interdisciplinary Graduate School (IGS), School of Physical and Mathematical Sciences, School of Biological Sciences, NTU Institute for Health Technologies, Temasek Life Sciences Laboratory |
| Rok vydání: | 2019 |
| Předmět: |
Peptide Nucleic Acids
Pyrimidine Stereochemistry Base pair Biological sciences [Science] RNA DNA Models Biological Biochemistry humanities Triplex-forming Oligonucleotides Nucleobase chemistry.chemical_compound Double-stranded RNA binding chemistry Duplex (building) Nucleic acid Nucleic Acid Conformation Computer Simulation Base Pairing Peptide Nucleic-acids RNA Double-Stranded |
| Zdroj: | Biochemistry. 58:1319-1331 |
| ISSN: | 1520-4995 0006-2960 |
| DOI: | 10.1021/acs.biochem.8b01313 |
| Popis: | Chemically modified peptide nucleic acids (PNAs) show great promise in the recognition of RNA duplexes by major-groove PNA·RNA–RNA triplex formation. Triplex formation is favored for RNA duplexes with a purine tract within one of the RNA duplex strands, and is severely destabilized if the purine tract is interrupted by pyrimidine residues. Here, we report the synthesis of a PNA monomer incorporated with an artificial nucleobase S, followed by the binding studies of a series of S-modified PNAs. Our data suggest that an S residue incorporated into short 8-mer dsRNA-binding PNAs (dbPNAs) can recognize internal Watson–Crick C-G and U-A, and wobble U-G base pairs (but not G-C, A-U, and G-U pairs) in RNA duplexes. The short S-modified PNAs show no appreciable binding to DNA duplexes or single-stranded RNAs. Interestingly, replacement of the C residue in an S·C-G triple with a 5-methyl C results in the disruption of the triplex, probably due to a steric clash between S and 5-methyl C. Previously reported PNA E base shows recognition of U-A and A-U pairs, but not a U-G pair. Thus, S-modified dbPNAs may be uniquely useful for the general recognition of RNA U-G, U-A, and C-G pairs. Shortening the succinyl linker of our PNA S monomer by one carbon atom to have a malonyl linker causes a severe destabilization of triplex formation. Our experimental and modeling data indicate that part of the succinyl moiety in a PNA S monomer may serve to expand the S base forming stacking interactions with adjacent PNA bases. Ministry of Education (MOE) Nanyang Technological University We thank Prof. Tom Brown for providing us a detailed protocol for the synthesis of the S base. This work was supported by NTU start-up grant, Singapore Ministry of Education (MOE) Tier 1 grants (RGT3/13, RG42/15, and RG152/17), and MOE Tier 2 grants (MOE2013-T2-2-024 and MOE2015-T2-1-028) to G.C. The work was also supported by MOE Tier 1 (RG126/16 and RG31/18) and MOE Tier 2 (MOE2018-T2-1-033) to K.X. |
| Databáze: | OpenAIRE |
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