Structure and protein recognition of G-quadruplexes

G-rich oligonucleotides can adopt non-canonical secondary structures called G-quadruplexes (G4s) which are biologically relevant and found in applications and nanotechnology. Due to the high structural polymorphism, it is still a challenge to specifically target different G4 structures. In this stud...

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Bibliographic Details
Main Author: Ngo, Khac Huy
Other Authors: Phan Anh Tuan
Format: Thesis-Doctor of Philosophy
Language:English
Published: Nanyang Technological University 2023
Subjects:
Online Access:https://hdl.handle.net/10356/164358
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Institution: Nanyang Technological University
Language: English
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Summary:G-rich oligonucleotides can adopt non-canonical secondary structures called G-quadruplexes (G4s) which are biologically relevant and found in applications and nanotechnology. Due to the high structural polymorphism, it is still a challenge to specifically target different G4 structures. In this study, different biophysical, biochemical, and structural techniques (CD, ITC, gel electrophoresis, enzymatic assay NMR spectroscopy, X-ray crystallography) and nucleic acid/protein/peptide engineering were applied to: i) expand our understanding of G4 diversity including base stacking, interlocking, and A•G•G•G•G pentad formation; ii) study the molecular basis for G4 recognition by proteins; iii) engineer G4-binding proteins/peptides for various applications including stable cyclic peptide or engineered enzyme for G4s targeting. The findings from this study provide a better understanding of G4 structures and their recognition by proteins.