Synthesis and application of imidazoquinoline TLR7/8 agonists conjugated with polyphosphazene polymers

Bc. Konstantin KOSENKO

Diplomová práce

Abstract:

The focus of this thesis was the preparation of a novel imidazoquinoline ligand and its conjugation with biodegradable PGA polyphosphazene. This conjugate has the potential to overcome certain limitations associated with the application of immune response modifiers such as resiquimod. Another part of the thesis is dedicated to studying the mechanistic differences between resiquimod and the novel agonist SA-401. Cell culture and biochemical experiments were performed to prepare samples suitable for MS proteomics, which can theoretically provide a comprehensive overview of these differences. Furthermore, we utilized bioinformatics and molecular dynamics simulations to supplement the analysis and evaluate the differences between these ligands.

Abstract:

The focus of this thesis was the preparation of a novel imidazoquinoline ligand and its conjugation with biodegradable PGA polyphosphazene. This conjugate has the potential to overcome certain limitations associated with the application of immune response modifiers such as resiquimod. Another part of the thesis is dedicated to studying the mechanistic differences between resiquimod and the novel agonist SA-401. Cell culture and biochemical experiments were performed to prepare samples suitable for MS proteomics, which can theoretically provide a comprehensive overview of these differences. Furthermore, we utilized bioinformatics and molecular dynamics simulations to supplement the analysis and evaluate the differences between these ligands.

Keywords

Organic chemistry, polymer chemistry, cancer, immunotherapy, Toll-like receptor agonists, polyphosphazenes

Jazyk práce: angličtina

Datum vytvoření / odevzdání či podání práce: 17. 9. 2025

Obhajoba závěrečné práce

• Vedoucí: prof. Dr. Wolfgang Schöfberger

JIHOČESKÁ UNIVERZITA V ČESKÝCH BUDĚJOVICÍCH

Přírodovědecká fakulta

Magisterský studijní program / obor:
Biological Chemistry / Biological Chemistry