Sequence- and structure-specific targeting of RNAs by short nucleobase-modified dsRNA-Binding PNAs Incorporating A-U pair-recognizing fluorescent light-up benzothiophene uracil and G-C pair-recognizing guanidinium
The structures of RNAs determine their functions including protein coding, catalysis, and gene regulation. RNAs are emerging as important therapeutic targets and diagnosis biomarkers. Compared to targeting RNAs through duplex formation, targeting the pre-formed dsRNA regions through structure-specif...
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| Format: | Thesis-Doctor of Philosophy |
| Language: | English |
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Nanyang Technological University
2020
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| Online Access: | https://hdl.handle.net/10356/137354 |
| _version_ | 1826123722457612288 |
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| author | Shivakumar Krishna Manchugondanahalli |
| author2 | Chen Gang |
| author_facet | Chen Gang Shivakumar Krishna Manchugondanahalli |
| author_sort | Shivakumar Krishna Manchugondanahalli |
| collection | NTU |
| description | The structures of RNAs determine their functions including protein coding, catalysis, and gene regulation. RNAs are emerging as important therapeutic targets and diagnosis biomarkers. Compared to targeting RNAs through duplex formation, targeting the pre-formed dsRNA regions through structure-specific triplex formation provides a complementary RNA probing/targeting strategy. However, triplex formation through Hoogsteen hydrogen bonding for all base pairs at near-physiological conditions is relatively challenging. We have developed a second-generation modified btU PNA monomer derived from uracil, which recognizes the Watson–Crick A-U base pair and shows fluorescence light-up effect upon binding to dsRNAs. In addition, we developed a novel PNA R monomer for the sequence and structure specific recognition of Watson–Crick G-C base pairs in dsRNAs under physiological pH conditions. Our work provides a modular PNA-based platform for the recognition of biomedically important RNAs for applications in diagnosis and therapeutics. |
| first_indexed | 2024-10-01T06:08:59Z |
| format | Thesis-Doctor of Philosophy |
| id | ntu-10356/137354 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:08:59Z |
| publishDate | 2020 |
| publisher | Nanyang Technological University |
| record_format | dspace |
| spelling | ntu-10356/1373542023-02-28T23:48:36Z Sequence- and structure-specific targeting of RNAs by short nucleobase-modified dsRNA-Binding PNAs Incorporating A-U pair-recognizing fluorescent light-up benzothiophene uracil and G-C pair-recognizing guanidinium Shivakumar Krishna Manchugondanahalli Chen Gang School of Physical and Mathematical Sciences rnachen@ntu.edu.sg Science::Chemistry The structures of RNAs determine their functions including protein coding, catalysis, and gene regulation. RNAs are emerging as important therapeutic targets and diagnosis biomarkers. Compared to targeting RNAs through duplex formation, targeting the pre-formed dsRNA regions through structure-specific triplex formation provides a complementary RNA probing/targeting strategy. However, triplex formation through Hoogsteen hydrogen bonding for all base pairs at near-physiological conditions is relatively challenging. We have developed a second-generation modified btU PNA monomer derived from uracil, which recognizes the Watson–Crick A-U base pair and shows fluorescence light-up effect upon binding to dsRNAs. In addition, we developed a novel PNA R monomer for the sequence and structure specific recognition of Watson–Crick G-C base pairs in dsRNAs under physiological pH conditions. Our work provides a modular PNA-based platform for the recognition of biomedically important RNAs for applications in diagnosis and therapeutics. Doctor of Philosophy 2020-03-18T06:30:03Z 2020-03-18T06:30:03Z 2020 Thesis-Doctor of Philosophy Shivakumar Krishna Manchugondanahalli. (2020). Sequence- and structure-specific targeting of RNAs by short nucleobase-modified dsRNA-Binding PNAs Incorporating A-U pair-recognizing fluorescent light-up benzothiophene uracil and G-C pair-recognizing guanidinium. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/137354 10.32657/10356/137354 en This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0). application/pdf Nanyang Technological University |
| spellingShingle | Science::Chemistry Shivakumar Krishna Manchugondanahalli Sequence- and structure-specific targeting of RNAs by short nucleobase-modified dsRNA-Binding PNAs Incorporating A-U pair-recognizing fluorescent light-up benzothiophene uracil and G-C pair-recognizing guanidinium |
| title | Sequence- and structure-specific targeting of RNAs by short nucleobase-modified dsRNA-Binding PNAs Incorporating A-U pair-recognizing fluorescent light-up benzothiophene uracil and G-C pair-recognizing guanidinium |
| title_full | Sequence- and structure-specific targeting of RNAs by short nucleobase-modified dsRNA-Binding PNAs Incorporating A-U pair-recognizing fluorescent light-up benzothiophene uracil and G-C pair-recognizing guanidinium |
| title_fullStr | Sequence- and structure-specific targeting of RNAs by short nucleobase-modified dsRNA-Binding PNAs Incorporating A-U pair-recognizing fluorescent light-up benzothiophene uracil and G-C pair-recognizing guanidinium |
| title_full_unstemmed | Sequence- and structure-specific targeting of RNAs by short nucleobase-modified dsRNA-Binding PNAs Incorporating A-U pair-recognizing fluorescent light-up benzothiophene uracil and G-C pair-recognizing guanidinium |
| title_short | Sequence- and structure-specific targeting of RNAs by short nucleobase-modified dsRNA-Binding PNAs Incorporating A-U pair-recognizing fluorescent light-up benzothiophene uracil and G-C pair-recognizing guanidinium |
| title_sort | sequence and structure specific targeting of rnas by short nucleobase modified dsrna binding pnas incorporating a u pair recognizing fluorescent light up benzothiophene uracil and g c pair recognizing guanidinium |
| topic | Science::Chemistry |
| url | https://hdl.handle.net/10356/137354 |
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