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Title: Nucleic acid structure and conjugation for drug design
Authors: Tan, Derrick Jing Yang
Keywords: Science::Chemistry
Issue Date: 2020
Publisher: Nanyang Technological University
Source: Tan, D. J. Y. (2020). Nucleic acid structure and conjugation for drug design. Doctoral thesis, Nanyang Technological University, Singapore.
Abstract: 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.
Rights: This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
Fulltext Permission: embargo_20230608
Fulltext Availability: With Fulltext
Appears in Collections:SPMS Theses

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