Dokument: Functional Calix[n]arenes as Building Blocks for the Solid-Phase Polymer Synthesis of Multivalent Glycocalix[n]arenes

Titel:	Functional Calix[n]arenes as Building Blocks for the Solid-Phase Polymer Synthesis of Multivalent Glycocalix[n]arenes
Weiterer Titel:	Funktionelle Calix[n]arene als Bausteine für die Festphasen-Polymersynthese multivalenter Glycocalix[n]arene
URL für Lesezeichen:	https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=72307
URN (NBN):	urn:nbn:de:hbz:061-20260302-125138-1
Kollektion:	Dissertationen
Sprache:	Englisch
Dokumententyp:	Wissenschaftliche Abschlussarbeiten » Dissertation
Medientyp:	Text
Autor:	Kayser, Alisa Isabel [Autor]
Dateien:	[Dateien anzeigen] Adobe PDF [Details] 23,44 MB in einer Datei [ZIP-Datei erzeugen] Dateien vom 16.02.2026 / geändert 21.02.2026
Beitragende:	Prof. Dr. Laura Hartmann [Gutachter] Prof. Dr. Delaittre, Guillaume [Gutachter]
Stichwörter:	Calix[n]arene, Solid-Phase Synthesis, Glycoconjugates
Dewey Dezimal-Klassifikation:	500 Naturwissenschaften und Mathematik » 540 Chemie
Beschreibung:	Carbohydrates play a pivotal role in nature as recognition markers, mediating a variety of biological processes. Their counterparts are carbohydrate-binding proteins, such as lectins and enzymes, which specifically recognize glycans. However, the individual carbohydrate-protein interactions are typically weak, which is why multivalent interactions are commonly employed by nature to achieve sufficient binding avidity. This principle is also explored by scientists generating so-called multivalent glycomimetic compounds, which can help to gain a deeper understanding of the glycan-protein interactions. Among these, calix[n]arenes have emerged as promising scaffolds due to their structural versatility and synthetic accessibility. This thesis focused on integrating calix[n]arene motifs into the solid-phase polymer synthesis (SPPoS) approach established by Hartmann et al., enabling the sequence-defined synthesis of glycocalix[n] arene-polymer conjugates. The first part of this thesis established a robust and straightforward synthetic strategy. The synthetic route was demonstrated for a first set of homo- and heteromultivalent glycocalix[4]arene. These compounds were further evaluated in a bacterial adhesion inhibition assay. Based on this, an advanced application of the modular glycocalix[4]arenes by attaching them onto ultrasmall gold nanoparticles (GNPs) was explored. It was reasoned that this could result in an even increased inhibitory potential against bacterial adhesion. Additionally, a key aspect of this part of the project was to achieve control over the ligand arrangement on the nanoparticle surface. A second set of glycocalix[4]arenes was synthesized, exhibiting alkyne functionalities positioned either at the upper or lower rim, allowing for an attachment to the azide-functionalized GNPs via copper-catalyzed azide-alkyne cycloaddition (CuAAC) in a single or multiple fashion. The second part of this thesis expanded the scope of target proteins beyond lectins to carbohydrate-processing enzymes. While multivalent ligands have already been extensively explored for lectin targeting, their potential as regulators or inhibitors of enzymes remains relatively unexplored. In this work, the de-N-glycosylating enzyme N-glycanase-1 (NGLY1), which is known to interact with high-mannose glycans, was investigated as a potential target. To test this hypothesis, the mannose-functionalized glycocalix[4]arene derivatives were additionally equipped with a biotin tag to facilitate bioanalytical studies. However, none of the conducted assays showed a selective binding of the ligands. The synthetic strategy was further enhanced with a split-and-combine approach to generate bispecific glycocalix[4]arene dimers. This approach allowed for the combination of two distinct glycocalix[4]arene units in a single structure, offering the ability to simultaneously target different carbohydrate-binding proteins. The model lectins Concanavalin A (Con A) and Peanut Agglutinin (PNA) were chosen, and the bispecific binding capability of a heteromultivalent dimer to both lectins was demonstrated via turbidity and precipitation assays. In the last part of this thesis calix[5]arenes, a higher homolog of calix[4]arenes, were explored as building block for SPPoS. Thereby introducing the additional structural feature of conformational flexibility, which may allow ligands to better adapt to the structural environment of their target proteins through a so-called induced fit. The primary focus was on the development of sialic acid-functionalized glycocalix[5]arenes as potential inhibitors of viral attachment proteins, specifically targeting the VP1 capsid protein of polyomaviruses. A series of glycocalix[5]arene derivatives with varying linker lengths and valency were synthesized to evaluate the influence of these parameters on binding interactions. In conclusion, this thesis presents a versatile and modular synthetic approach to develop tailor-made glycocalix[n]arenes as demonstrated in multiple projects for various target proteins.
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:	02.03.2026
Dateien geändert am:	02.03.2026
Promotionsantrag am:	25.09.2025
Datum der Promotion:	28.11.2025