| Author: | Zhang, Junhui |
| Title: | Chiral lanthanide probes for protein studies |
| Advisors: | Law, Ga-lai (ABCT) Wong, Wing-tak (ABCT) |
| Degree: | Ph.D. |
| Year: | 2023 |
| Subject: | Proteins Molecular probes Hong Kong Polytechnic University -- Dissertations |
| Department: | Department of Applied Biology and Chemical Technology |
| Pages: | xiii, 253 pages : color illustrations |
| Language: | English |
| Abstract: | Revealing protein interactions in multiple biological activities is vital for disease therapy and drug discovery. Extensive research related to protein probe has been conducted in recent decades. However, most of them are limited to certain aspects, for instance, stability, targeting ability, sensitivity and photophysical performance. Herein, chiral lanthanide complexes were designed and synthesized in this thesis for bioimaging and protein studies. In chapter 1, the fundamental lanthanide properties were introduced. Lanthanide properties and reasons of choosing lanthanide complexes for protein studies were mentioned. Chapter 2 focused on the design and syntheses of chiral DOTAs with various chiral moieties introduced to the macrocyclic backbone, which served as the platform of chiral lanthanide probes. The relaxivity and protonation constants of chiral DOTAs were investigated. There are numerous applications for the chiral DOTA derivatives. First, the probes were designed for bioimaging purposes. With suitable light harvesting system, such as organic chromophore, conjugated to the macrocyclic backbone, energy can transfer to the lanthanide metal center through antenna effect efficiently. In chapter 3, the photophysical properties of a series of highly emissive chiral europium probes for imaging applications were studied and discussed. The photoluminescence and circularly polarized luminescence (CPL) of these probes were investigated under various biological conditions. To further examine their CPL properties, external magnetic field was applied. Surprisingly, significant magnetic responses, which was still rare, were recorded. Despite highly emissive europium probes were obtained, the UV absorption maxima of such probes were not ideal for clinical use. The UV absorption maximum of emissive probe should be close to the visible region, which matches the working range of most of the fluorescence microscopes. Hence, the chromophore was redesigned for optimal excitation wavelength. The modifications of chromophores were then conducted in chapter 4. In addition, specific chiral lanthanide probes were also designed for the inflammation-related glycoproteins. The probe was based on the DO2A derivatives. In the preliminary study, it gave significant growth in emission intensity after titrating to glycoprotein. Methods were discussed to distinguish between the isomers of these DO2A derivatives in this chapter. The chiral DOTA platform can also apply to magnetic resonance imaging (MRI) and NMR. In chapter 5, the chiral DOTA derivatives were designed and synthesized as MRI probes for protein of interest. Through studying the changes in relaxivity and luminescence intensity, the interactions between the probe and protein could be revealed. |
| Rights: | All rights reserved |
| Access: | open access |
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