Dokument: Synthesis and Characterization of Polymeric Glycoconjugate Mimetics
| Titel: | Synthesis and Characterization of Polymeric Glycoconjugate Mimetics | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=71854 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20260120-122631-3 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Feldhof, Melina Irene [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. Hartmann, Laura [Gutachter] apl. Prof. Dr. Smits, Sander [Gutachter] | |||||||
| Dewey Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik » 540 Chemie | |||||||
| Beschreibung: | The glycocalyx is a carbohydrate-dense layer on endothelial cells mediating biological functions like cellular communication and pathogen detection. Specific glycan motifs initiate contact with cells or during pathogen adhesion. Many underlying mechanisms remain unclear due to limited access to complex glycan conjugates, given their instability and isolation challenges. Glycomimetics offer a promising alternative to study natural glycan motifs' biological functions. This thesis develops synthetic strategies combining synthetic and biopolymers as scaffolds for glycomimetic presentation.
In the first part, a new strategy for protein glycosylation was established using proteins as macroinitiators in thiol-induced, light-activated controlled radical polymerization (TIRP). This approach was applied using bovine serum albumin (BSA) and candida rugosa lipase (CRL) proteins for grafting-from at specific cysteine residues. Hydrophilic poly(2-hydroxyethyl acrylate), temperature-responsive poly(N-isopropylacrylamide) (pNIPAM) and glycopolymers were attached to the protein. The protein-polymer conjugates preserved their natural structure and function. The enzyme conjugates maintained activity, with pNIPAM conjugates showing enhanced activity after temperature-induced aggregation. BSA-glycopolymer conjugates enabled surface coatings through physisorption on glass slides, providing access to glycosurfaces for protein screening. Further, a rebridging agent was introduced to enable a second polymer's addition through TIRP, allowing site-specific conjugation to native proteins. pNIPAM-decorated BSA containing this agent followed by TIRP produces defined pNIPAM-BSA-glycopolymer conjugates. These structures form nanoclusters with a glycopolymer corona above LCST and enable reversible formation of a protein corona through glycan-lectin interactions, creating multilayered nanoparticles. This approach creates dual-responsive particles that disassemble either stepwise or in one step, triggered by temperature below LCST or competing ligands. Aggregation behavior can be tuned by mixing different pNIPAM-protein-glycopolymer conjugates, where controlling the binding/non-binding glycopolymer ratio determines particle corona or cluster formation. Glycan-protein-conjugates use proteins as scaffolds for high-density presentation of branched glycan side chains, forming mucins that protect epithelial surfaces against pathogens. The mucin mimetics developed in the second part replicate natural structures using double-brushed polymer topology. By combining solid-phase synthesis of glycooligomers with polyactive ester frameworks and subsequent sulfation, a library of linear, brushed, and double-brushed glycopolymers was created. This approach enables control over side chain parameters, carbohydrate type, and sulfation. Together with Prof. Karg and Dr. Balzer's groups, the physicochemical properties of these mimetics were analyzed via scattering techniques and force spectroscopy. Only double-brush architecture glycomimetic polymers effectively replicate mucin-specific properties like extended conformation and surface adhesion. In the third part, fully synthetic glycopolymers with star-like topology were synthesized combining sequence-defined macroinitiators through solid phase chemistry and TIRP. Compared to known initiators, the macroinitiators enable three-site TIRP under controlled conditions. This core-first method offers versatility in designing core and polymer structures, allowing control over chain number, density, and length. These star-shape glycopolymers show potential for drug delivery and as antibacterial and antiviral therapeutics. | |||||||
| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät » WE Chemie » Organische Chemie und Makromolekulare Chemie | |||||||
| Dokument erstellt am: | 20.01.2026 | |||||||
| Dateien geändert am: | 20.01.2026 | |||||||
| Promotionsantrag am: | 17.04.2025 | |||||||
| Datum der Promotion: | 27.11.2025 |
