Nucleic acid structure and conjugation for drug design
Nucleic acids can adopt diverse secondary structures, one of which is the four-stranded G-quadruplex (G4). The G4s have been widely studied as anticancer targets where their stabilization by ligands were shown to impact downstream biological processes. Recent discoveries of G4 sub-types, such as qua...
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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/10356/143056 |
| _version_ | 1826110305618362368 |
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| author | Tan, Derrick Jing Yang |
| author2 | Phan Anh Tuan |
| author_facet | Phan Anh Tuan Tan, Derrick Jing Yang |
| author_sort | Tan, Derrick Jing Yang |
| collection | NTU |
| description | Nucleic acids can adopt diverse secondary structures, one of which is the four-stranded G-quadruplex (G4). The G4s have been widely studied as anticancer targets where their stabilization by ligands were shown to impact downstream biological processes. Recent discoveries of G4 sub-types, such as quadruplex-duplex hybrid (QDH) and G4 with vacant sites, provide additional structural features exploitable by ligands to improve their selectivity. This thesis investigates the structural features of QDHs found in PIM1 oncogene. In addition, strategies for targeting of G4 with vacant sites were also developed. The results provide insights for future design of ligand and targeting these structures. Nucleic acids can also act as therapeutic agents where conjugation with various peptides can improve their pharmacokinetic properties. However, the conflicting synthetic methods of the two types of oligomers often limit the generation of such chimeric molecules. A novel method has been developed for regioselective generation of peptide/protein-oligonucleotide conjugates. |
| first_indexed | 2024-10-01T02:32:14Z |
| format | Thesis-Doctor of Philosophy |
| id | ntu-10356/143056 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T02:32:14Z |
| publishDate | 2020 |
| publisher | Nanyang Technological University |
| record_format | dspace |
| spelling | ntu-10356/1430562023-02-28T23:32:35Z Nucleic acid structure and conjugation for drug design Tan, Derrick Jing Yang Phan Anh Tuan School of Physical and Mathematical Sciences PhanTuan@ntu.edu.sg Science::Chemistry::Biochemistry Nucleic acids can adopt diverse secondary structures, one of which is the four-stranded G-quadruplex (G4). The G4s have been widely studied as anticancer targets where their stabilization by ligands were shown to impact downstream biological processes. Recent discoveries of G4 sub-types, such as quadruplex-duplex hybrid (QDH) and G4 with vacant sites, provide additional structural features exploitable by ligands to improve their selectivity. This thesis investigates the structural features of QDHs found in PIM1 oncogene. In addition, strategies for targeting of G4 with vacant sites were also developed. The results provide insights for future design of ligand and targeting these structures. Nucleic acids can also act as therapeutic agents where conjugation with various peptides can improve their pharmacokinetic properties. However, the conflicting synthetic methods of the two types of oligomers often limit the generation of such chimeric molecules. A novel method has been developed for regioselective generation of peptide/protein-oligonucleotide conjugates. Doctor of Philosophy 2020-07-24T01:04:05Z 2020-07-24T01:04:05Z 2020 Thesis-Doctor of Philosophy Tan, D. J. Y. (2020). Nucleic acid structure and conjugation for drug design. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/143056 10.32657/10356/143056 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::Biochemistry Tan, Derrick Jing Yang Nucleic acid structure and conjugation for drug design |
| title | Nucleic acid structure and conjugation for drug design |
| title_full | Nucleic acid structure and conjugation for drug design |
| title_fullStr | Nucleic acid structure and conjugation for drug design |
| title_full_unstemmed | Nucleic acid structure and conjugation for drug design |
| title_short | Nucleic acid structure and conjugation for drug design |
| title_sort | nucleic acid structure and conjugation for drug design |
| topic | Science::Chemistry::Biochemistry |
| url | https://hdl.handle.net/10356/143056 |
| work_keys_str_mv | AT tanderrickjingyang nucleicacidstructureandconjugationfordrugdesign |