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postgraduate thesis: Introducing aldehyde functionality to proteins using ligand-directed affinity labeling and target-guided selection of DNA encoded libraries for macrocycle ligand discovery
Title | Introducing aldehyde functionality to proteins using ligand-directed affinity labeling and target-guided selection of DNA encoded libraries for macrocycle ligand discovery |
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Authors | |
Issue Date | 2022 |
Publisher | The University of Hong Kong (Pokfulam, Hong Kong) |
Citation | Song, Y. [宋一男]. (2022). Introducing aldehyde functionality to proteins using ligand-directed affinity labeling and target-guided selection of DNA encoded libraries for macrocycle ligand discovery. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. |
Abstract | Protein labeling strategies have been served as powerful tools in studying the cellular localizations, structures, dynamics and functions of target proteins for the past decades. From the fusion green fluorescent protein (GFP) tags published in 1990s to abundant of innovative protein labeling technologies nowadays, significant development and conspicuous achievements have been accomplished.
In the first part of this thesis, we were trying to develop a new class of bifunctional probes but with trifunctional capacities based on affinity guided protein labeling that can realize the traceless aldehyde modification of target proteins both in vitro and in vivo. And in this manner, we hope to realize some distinct applications with the help of special chemical properties of aldehydes.
Besides, with the experience in developing proximity effect based chemistries in biosystems, in the second part of this thesis, we were focusing on the elevation of current selection methods of potential macrocycle ligands via DNA encoded chemical libraries.
In contrast with the traditional selection methods which needs pre-cyclization of each candidate, we proposed a target-guided selection method for DNA encoded macrocycle precursor library (DEMPL) which can realize the selection of macrocycles without pre-cyclization. Similar to the kinetic target-guided synthesis (KTGS), the irreversible cleavage of the reactive linker via protein templated cyclization will release the respective DNA barcodes of cyclized precursors which can then be amplified and deconvoluted. Thus, the selection of macrocycles can be achieved with DEMPL instead of traditional macrocycle libraries bringing fresh opportunities in “Drugging the undruggable targets”. |
Degree | Doctor of Philosophy |
Subject | Aldehydes Proteins - Affinity labeling |
Dept/Program | Chemistry |
Persistent Identifier | http://hdl.handle.net/10722/325775 |
DC Field | Value | Language |
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dc.contributor.author | Song, Yinan | - |
dc.contributor.author | 宋一男 | - |
dc.date.accessioned | 2023-03-02T16:32:44Z | - |
dc.date.available | 2023-03-02T16:32:44Z | - |
dc.date.issued | 2022 | - |
dc.identifier.citation | Song, Y. [宋一男]. (2022). Introducing aldehyde functionality to proteins using ligand-directed affinity labeling and target-guided selection of DNA encoded libraries for macrocycle ligand discovery. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. | - |
dc.identifier.uri | http://hdl.handle.net/10722/325775 | - |
dc.description.abstract | Protein labeling strategies have been served as powerful tools in studying the cellular localizations, structures, dynamics and functions of target proteins for the past decades. From the fusion green fluorescent protein (GFP) tags published in 1990s to abundant of innovative protein labeling technologies nowadays, significant development and conspicuous achievements have been accomplished. In the first part of this thesis, we were trying to develop a new class of bifunctional probes but with trifunctional capacities based on affinity guided protein labeling that can realize the traceless aldehyde modification of target proteins both in vitro and in vivo. And in this manner, we hope to realize some distinct applications with the help of special chemical properties of aldehydes. Besides, with the experience in developing proximity effect based chemistries in biosystems, in the second part of this thesis, we were focusing on the elevation of current selection methods of potential macrocycle ligands via DNA encoded chemical libraries. In contrast with the traditional selection methods which needs pre-cyclization of each candidate, we proposed a target-guided selection method for DNA encoded macrocycle precursor library (DEMPL) which can realize the selection of macrocycles without pre-cyclization. Similar to the kinetic target-guided synthesis (KTGS), the irreversible cleavage of the reactive linker via protein templated cyclization will release the respective DNA barcodes of cyclized precursors which can then be amplified and deconvoluted. Thus, the selection of macrocycles can be achieved with DEMPL instead of traditional macrocycle libraries bringing fresh opportunities in “Drugging the undruggable targets”. | - |
dc.language | eng | - |
dc.publisher | The University of Hong Kong (Pokfulam, Hong Kong) | - |
dc.relation.ispartof | HKU Theses Online (HKUTO) | - |
dc.rights | The author retains all proprietary rights, (such as patent rights) and the right to use in future works. | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject.lcsh | Aldehydes | - |
dc.subject.lcsh | Proteins - Affinity labeling | - |
dc.title | Introducing aldehyde functionality to proteins using ligand-directed affinity labeling and target-guided selection of DNA encoded libraries for macrocycle ligand discovery | - |
dc.type | PG_Thesis | - |
dc.description.thesisname | Doctor of Philosophy | - |
dc.description.thesislevel | Doctoral | - |
dc.description.thesisdiscipline | Chemistry | - |
dc.description.nature | published_or_final_version | - |
dc.date.hkucongregation | 2022 | - |
dc.identifier.mmsid | 991044649999603414 | - |